Biochemistry - First Aid Flashcards
(911 cards)
1
Q
Chromatin Structure
A
2
Q
DNA exists in the condensed _____ form to fit into the nucleus.
A
chromatin
3
Q
DNA loops twice around a _____ to form a _____ (“beads on a string”).
A
histone octamer
nucleosome
4
Q
H1 binds to the _____ and to the _____, thereby stabilizing the _____.
A
nucleosome
linker DNA
chromatin fiber
5
Q
_____ groups give DNA a (-) charge.
A
Phosphate
6
Q
_____ give histones a (+) charge.
A
Lysine
Arginine
7
Q
In _____, DNA condenses to form _____.
A
mitosis
chromosomes
8
Q
DNA and histone synthesis occurs during the _____.
A
S phase
9
Q
Mitochondria have their own DNA which is _____ and does not utilize _____.
A
circular
histones
10
Q
Chromatin:
- condensed
- darker on EM
- transcriptionally inactive
- sterically inaccessible
- ↑ methylation
- ↓ acetylation
A
heterochromatin
Hetero-Chromatin = Highly Condensed
11
Q
_____ are inactive X chromosomes which may be visible on the periphery of the nucleus.
A
Barr bodies
*heterochromatin
12
Q
Chromatin:
- less condensed
- lighter on EM
- transcriptionally active
- sterically inaccessible
A
euchromatin
Euchromatin = Expressed
13
Q
_____ changes the expression of a DNA segment without changing the sequence.
A
DNA Methylation
14
Q
_____ is involved with genomic imprinting, X-chromosome inactivation, repression of transposable elements, aging and carcinogenesis.
A
DNA Methylation
15
Q
Methylation within _____ typically represses gene transcription.
A
gene promoter (CpG islands)
CpG Methylation Makes DNA Mute
16
Q
_____ usually causes reversible transcriptional suppression, but can also cause activation depending on location of methyl groups.
A
Histone Methylation
Histone Methylation Mostly Makes DNA Mute
17
Q
_____ relaxes DNA coiling, allowing for transcription.
A
Histone Acetylation
Histone Acetylation makes DNA Active
18
Q
Purine
A
19
Q
Pyrimidine
A
20
Q
Nucleoside Composition
A
NucleoSide = base + (deoxy)ribose (Sugar)
21
Q
Nucleotide Composition
A
NucleoTide = base + (deoxy)ribose + phosphaTe
*linked by 3’-5’ phosphodiester bond
22
Q
5’ end of incoming nucleotide bears the _____.
A
triphosphate
*energy source for the bond
23
Q
Triphosphate bond is the target of _____ attack.
A
3’ hydroxyl
24
Q
Purines
A
A, G - 2 rings
PURe As Gold
25
Pyrimidines
C, U, T - 1 ring
**CUT** the **PY** (pie)
26
Deamination of cytosine forms \_\_\_\_\_.
uracil
27
Deamination of adenine forms \_\_\_\_\_.
hypoxanthine
28
Deamination of guanine forms \_\_\_\_\_.
xanthine
29
Deamination of 5-methylcytosine forms \_\_\_\_\_.
thymine
30
Uracil is found in \_\_\_\_\_.
RNA
31
Thymine is found in \_\_\_\_\_.
DNA
32
Methylation of uracil makes \_\_\_\_\_.
thymine
**THY**mine has me**THY**l
33
G-C bonds have _____ H bonds.
3
34
A-T bonds have _____ H bonds.
2
35
Higher G-C bonds means _____ of DNA.
higher melting T
**C**-**G** bonds are like **C**razy **G**lue
36
Amino Acids Essential for Purine Synthesis
**G**lycine
**A**spartate
**G**lutamine
Cats **Pur**r until they **GAG**
37
De novo Pyrimidine and Purine Synthesis
38
Pyrimidine Synthesis Blockers:
inhibits dihydroorotate dehydrogenase
Leflunomide
39
Pyrimidine Synthesis Blockers:
inhibits dihydrofolate reductase (↓ deoxythymidine monophosphate [dTMP])
Methotrexate (MTX) - humans
Trimethoprim (TMP) - bacteria
Pyrimethamine - protozoa
40
Pyrimidine Synthesis Blockers:
inhibits thymidylate synthase (↓ dTMP)
5-fluorouracil (5-FU)
5-FU + capecitabine = 5-F-dUMP
41
Purine Synthesis Blockers:
inhibit de novo purine synthesis
6-mercaptopurine (6-MP)
\*Azathioprine - prodrug
42
Purine Synthesis Blockers:
inhibit inosine monophosphate dehydrogenase
Mycophenolate
Ribavirin
43
Purine and Pyrimidine Synthesis Blockers:
inhibits ribonucleotide reductase
Hydroxyurea
44
Carbamoyl Phosphate Synthase I is found in the \_\_\_\_\_.
Mitochondria
CPS**1** = m**1**tochondria (urea cycle)
45
Carbamoyl Phosphate Synthase II is found in the \_\_\_\_\_.
Cytosol
CPS**2** = cy**TWO**sol
46
Purine Salvage Deficiencies
47
\_\_\_\_\_ is required for degradation of adenosine and deoxyadenosine.
Adenosine Deaminase (ADA)
48
In ADA deficiency, ↓ dATP → \_\_\_\_\_.
lymphotoxicity
49
Adenosine Deaminase Deficiency is one of the major causes of \_\_\_\_\_.
autosomal recessive SCID
50
\_\_\_\_\_ is caused by defective purine salvage due to absent HGPRT, which converts hypoxanthine to IMP and guanine to GMP.
Lesch-Nyhan Syndrome
51
\_\_\_\_\_ results in excess uric acid production and de novo purine synthesis.
Lesch-Nyhan Syndrome
52
Lesch-Nyhan Syndrome is an _____ disease.
X-linked recessive
53
Lesch-Nyhan Syndrome Findings
**HGPRT**
* **H**yperuricemia
* **G**out
* **P**issed off (aggression, self-mutilation)
* **R**etardation (intellectual disability)
* Dys**T**onia
54
Lesch-Nyhan Syndrome Treatment
Allopurinol
Febuxostat
55
Genetic Code Features
* Unambiguous
* Degenerate/Redundant
* Commaless, Non-Overlapping
* Universal
56
Genetic Code Features:
each codon specifies only 1 amino acid
Unambiguous
57
Genetic Code Features:
most amino acids are coded by multiple codons
Degenerate/Redundant
58
Codons that differ in the 3rd (\_\_\_\_\_) position may code for the same tRNA/amino acid.
wobble
59
Specific base pairing is usually required only in the _____ of the mRNA codon.
first 2 nucleotide positions
60
\_\_\_\_\_ are encoded by only 1 codon.
Methionine (AUG)
Tryptophan (UGG)
61
Genetic Code Features:
read from a fixed starting point as a continuous sequence of bases
Commaless, Non-Overlapping
62
Genetic Code Features:
genetic code is conserved throughout evolution
Universal
63
DNA Replication
64
In both prokaryotes and eukaryote, DNA replication is _____ and involves both _____ synthesis and occurs in the _____ direction.
* semiconservative
* continuous and discontinuous (Okazaki fragments)
* 5' → 3'
65
\_\_\_\_\_ is the particular consensus sequence of base pairs in genome where DNA replication begins.
Origin of Replication
\*prokaryotes - single
\*eukaryotes - multiple
66
\_\_\_\_\_ sequences are found in promoters and origins of replication.
AT-rich sequences
\*TATA box
67
The _____ is a Y-shaped region along the DNA template where leading and lagging straands are synthesized.
Replication Fork
68
\_\_\_\_\_ unwinds the DNA template at the replication fork.
Helicase
**H**elicase **H**alves DNA
69
\_\_\_\_\_ prevents DNA strands from reannealing.
Single-Stranded Binding Proteins
70
\_\_\_\_\_ create a single- or double-stranded break in the helix to add or remove supercoils.
DNA Topoisomerases (TOP)
71
In eukaryotes, _____ inhibit TOP I.
Irinotecan
Topotecan
72
In eukaryotes, _____ inhibit TOP II.
Etoposide
Teniposide
73
In prokaryotes, _____ inhibit TOP II (DNA Gyrase) and TOP IV.
Fluoroquinolones
74
\_\_\_\_\_ makes an RNA primer on which DNA Polymerase III can initiate replication.
Primase
75
\_\_\_\_\_ elongates the leading strand by adding deoxynucleotides to the 3' end.
DNA Polymerase III
\*only in prokaryotes
76
\_\_\_\_\_ elongates the lagging strand until it reaches the primer of the preceding fragment.
DNA Polymerase III
\*only in prokaryotes
77
DNA Polymerase III has _____ synthesis.
5' → 3'
78
DNA Polymerase III proofreads with _____ exonuclease.
3' → 5'
79
Drugs blocking DNA replication often have a _____ thereby preventing addition of the next nucleotide ("chain termination").
modified 3' OH
80
\_\_\_\_\_ degrades the RNA primer and replaces it with DNA.
DNA Polymerase I
\*only in prokaryotes
81
DNA Polymerase I excises the RNA primer with \_\_\_\_\_.
5' → 3' exonuclease
82
\_\_\_\_\_ catalyzes the formation of a phosphodiester bond within a strand of double-stranded DNA.
DNA Ligase
**L**igase **L**inks DNA
83
\_\_\_\_\_ joins the Okazaki fragments.
DNA Ligase
**L**igase **L**inks DNA
84
\_\_\_\_\_ is a reverse transcriptase (RNA-dependent DNA Polymerase) that adds DNA (TTAGGG) to 3' ends of chromosomes to avoid loss of genetic material with every duplication.
Telomerase
**T**elomerase **TAG**s for **G**reatness and **G**lory
\*only in eukaryotes
85
\_\_\_\_\_ is often dysregulated in cancer cells, allowing unlimited replication.
Telomerase
86
Severity of DNA Mutations
silent \<\< missense \< nonsense \< frameshift
87
Purine → Purine or Pyrimidine → Pyrimidine Mutation
Transition
88
Purine ⇆ Pyrimidine Mutation
Transversion
89
DNA Mutations:
nucleotide substitution but codes for same (synonymous) amino acid, often base in 3rd position of codon (tRNA wobble)
Silent
90
DNA Mutations:
nucleotide substitution resulting in changes amino acid (conservative if new amino acid is similar in chemical structure)
Missense
91
Sickle Cell Disease is caused by the \_\_\_\_\_.
substitution of glutamic acid with valine
\*missense
92
DNA Mutations:
nucleotide substitution resulting in early stop codon (UAA, UAG, UGA), usually results in nonfunctional protein
Nonsense
**Stop** the **Nonsense**!
93
DNA Mutations:
deletion or insertion of a number of nucleotides not divisible by 3, resulting in misreading of all nucleotides downstream
Frameshift
94
Duchenne Muscular Dystrophy and Tay-Sachs Disease is caused by _____ mutation.
Frameshift
95
Mutation at a _____ → retained intron in the mRNA → protein with impaired or altered function
splice site
96
Lac Operon Mechanism
97
Lac Operon and Glucose
98
Glucose is the preferred metabolic substrate in E. coli, but when glucose is absent and lactose is available, the _____ is activated to switch to lactose metabolism.
Lac Operon
99
Lac Operon Mechanism:
Low Glucose
↓ glucose → ↑ adenylate cyclase activity → ↑ generation of cAMP from ATP → activation of catabolite activator protein (CAP) → ↑ transcription
100
Lac Operon Mechanism:
High Glucose
↑ glucose → unbinds repressor protein from repressor/operator site → ↑ transcription
101
Single Strand DNA Repair:
specific endonucleases release the oligonucleotides containing damaged bases, DNA polymerase and ligase fill and reseal the gap
Nucleotide Excision Repair
102
Single Strand DNA Repair:
repairs bulky helix-distorting lesions
Nucleotide Excision Repair
103
Single Strand DNA Repair:
occurs in G1 phase of the cell cycle
Nucleotide Excision Repair
104
Single Strand DNA Repair:
defective in xeroderma pigmentosum (inability to repair DNA pyrimidine dimers cause by UV exposure) which causes dry skin, extreme light sensitivity and skin cancer
Nucleotide Excision Repair
105
Single Strand DNA Repair:
base-specific **G**lycosylase removes altered base and creates AP site (apurinic/apyramidinic), one or more nucleotides are removed by AP-**E**ndonuclease which cleaves the 5' end, **L**yase cleaves the 3' end, DNA **P**olymerase-β fills the gap and DNA **L**igase seals it
Base Excision Repair
**GEL PL**ease
106
Single Strand DNA Repair:
occurs throughout the cell cycle
Base Excision Repair
107
Single Strand DNA Repair:
important in the repair of spontaneous/toxic deamination
Base Excision Repair
108
Single Strand DNA Repair:
newly synthesized strand is recognized, mismatched nucleotides are removed and the gap is filled and resealed
Mismatch Repair
109
Single Strand DNA Repair:
occurs predominantly in the S phase of the cell cycle
Mismatch Repair
110
Single Strand DNA Repair:
defective in Lynch Syndrome (hereditary nonpolyposis colorectal cancer [HNPCC])
Mismatch Repair
111
Double Strand DNA Repair:
brings together 2 ends of DNA fragments to repair double-stranded breaks, no requirement for homology, some DNA may be lost
Nonhomologous End Joining
112
Double Strand DNA Repair:
defective in Ataxia Telangiectasia and Fanconi Anemia
Nonhomologous End Joining
113
Double Strand DNA Repair:
requires 2 homologous DNA duplexes, a strand from the damaged dsDNA is repaired using a complementary strand from the intact homologous dsDNA as a template, restores duplexes accurately without loss of nucleotides
Homologous Recombination
114
Double Strand DNA Repair:
defective in breast/ovarian cancers with BRCA1 mutation
Homologous Recombination
115
mRNA Start Codon
AUG
\*methionine - eukaryotes
\*N-formylmethionine (fMet) - prokaryotes
116
mRNA Stop Codons
UAA, UAG, UGA
117
Functional Organization of a Eukaryotic Gene
118
The _____ is the site where RNA Polymerase II and other transcriptions factors bind to DNA upstream from gene locus (AT-rich upstream sequence with TATA and CAAT boxes).
Promoter
119
\_\_\_\_\_ mutation commonly results in dramatic ↓ in level of gene transcription.
Promoter
120
The _____ is the DNA locus where regulatory proteins ("activators") bind → increasing expression of a gene on the same chromosome.
Enhancer
121
The _____ is the DNA locus where regulatory proteins ("repressors") bind → decreasing expression of a gene on the same chromosome.
Silencers
122
In eukaryotes, RNA Polymerase I makes \_\_\_\_\_, present only in the nucleolus.
rRNA
**r** = **r**ampant
\* most common
123
In eukaryotes, RNA Polymerase II makes \_\_\_\_\_, which is read 5' → 3'.
mRNA
**m** = **m**assive
\*largest
124
In eukaryotes, RNA Polymerase III makes \_\_\_\_\_.
tRNA
**t** = **t**iny
\*smallest
125
\_\_\_\_\_ opens DNA at the promoter site.
RNA Polymerase II
126
\_\_\_\_\_ found in _____ inhibits RNA Polymerase II and causes severe hepatotoxicity if ingested.
α-amanitin
Amanita phalloides (death cap mushrooms)
127
\_\_\_\_\_ inhibits RNA Polymerase in both prokaryotes and eukaryotes.
Actinomycin D
128
In prokaryotes, _____ (multisubunit complex) makes all 3 kinds of RNA.
1 RNA Polymerase
129
\_\_\_\_\_ inhibits DNA-dependent RNA Polymerase in prokaryotes.
Rifampin
130
RNA Processing in Eukaryotes
131
\_\_\_\_\_, the initial transcript in eukaryote RNA processing, is modified and becomes mRNA.
heterogenous nuclear RNA (hnRNA)
132
RNA Processing
1. capping of 5' end (addition of 7-methylguaanosine cap)
2. polyadenylation of 3' end (~ 200 A's)
3. splicing out of introns
133
Capped, tailed and spliced transcript is called \_\_\_\_\_.
mRNA
134
\_\_\_\_\_ is transported out of the nucleus into the cytosol, where it is translated.
mRNA
135
mRNA quality control occurs at \_\_\_\_\_, which contain exonucleases, decapping enzymes, and microRNAs.
cytoplasmic processing bodies (P-bodies)
136
mRNAs may be degraded or stored in _____ for future translation.
cytoplasmic processing bodies (P-bodies)
137
\_\_\_\_\_ Polymerase does not require a template.
Poly-A
138
Polyadenylation Signal
AAUAAA
139
Splicing of Pre-mRNA
140
\_\_\_\_\_ contain the actual genetic information coding for protein.
Exons
**Ex**ons **Ex**it and are **Ex**pressed.
141
\_\_\_\_\_ are intervening noncoding segments of DNA.
Introns
**In**trons **In**tervene **In** the nucleus.
142
\_\_\_\_\_ can produce a variety of products from a single hnRNA sequence.
Alternative Splicing
143
Alternative Splicing
144
\_\_\_\_\_ are small, conserved, noncoding RNA molecules that posttranscriptionally regulate gene expression by targeting the 3' untranslated region of specific mRNAs for degradation or translational repression.
MicroRNAs (miRNAs)
145
\_\_\_\_\_ has 75-90 nucleotides, 2° structure, cloverleaf form, and anticodon end is opposite 3' aminoacyl end.
tRNA
146
All tRNAs have _____ at the 3' end with a high percentage of chemically modified bases.
CCA
**C**an **C**arry **A**mino acids
147
The amino acid is covalently bound to the _____ of the tRNA.
3' end
148
The _____ of the tRNA contains the TΨC (ribothymidine, pseudouridine, cytidine) sequence necessary for tRNA-ribosome binding.
T-arm
**T**-arm **T**ethers tRNA to ribosome
149
The _____ of the tRNA contains dihydrouridine residues necessary for tRNA recognition by the correct aminoacyl-tRNA synthetase.
D-arm
**D**-arm **D**etects the aminoacyl-tRNA synthetase
150
The _____ is the amino acid acceptor site.
5'-CCA-3' (Acceptor Stem)
151
\_\_\_\_\_ scrutinizes the amino acid before and after it binds to tRNA.
Aminoacyl-tRNA Synthetase
152
If incorrect, the tRNA-amino acid bond is \_\_\_\_\_.
hydrolyzed
153
The tRNA-amino acid bond has energy for the formation of \_\_\_\_\_.
peptide bond
154
A mischarged tRNA reads the usual codon but \_\_\_\_\_.
inserts the wrong amino acid
155
\_\_\_\_\_ and _____ are responsible for the accuracy of amino acid selection.
* Aminoacyl-tRNA Synthetase
* binding of charged tRNA to the codon
156
tRNA charging requires \_\_\_\_\_.
ATP
**A**TP = tRNA **A**ctivation (charging)
157
tRNA Structure
158
Protein Synthesis Initiation: identify either the 5' cap or an internal ribosome entry site (IRES)
eukaryotic initiation factors (eIFs)
159
Protein Synthesis Initiation: can be located at many places in an mRNA, most often at the 5'UTR
internal ribosome entry site (IRES)
160
Protein Synthesis Initiation: help assemble the 40S ribosomal subunit with the initiator tRNA and are released when the mRNA and the ribosomal 60S subunit assemble with the complex
eukaryotic initiation factors (eIFs)
161
Protein synthesis initiation requires \_\_\_\_\_.
GTP
**G**TP = tRNA **G**ripping and **G**oing places (translocation)
162
Eukaryotic Ribosomal Subunits
40S + 60S → 80S
**E**ukaryotes = **E**ven
163
Prokaryotic Ribosomal Subunits
30S + 50S → 70S
pr**O**karyotes = **O**dd
164
Protein Elongation Process
1. Aminoacyl-tRNA binds to A site (except for initiator methinine), requires an elongation factor and GTP
2. rRNA ("ribozyme") catalyzes peptide bond formation, transfers growing polypeptide to amino acid in A site
3. Ribosome advances 3 nucleotides toward 3' end of mRNA, moving peptidyl tRNA to P site (translocation)
165
Protein Elongation Process: Step 1
Aminoacyl-tRNA binds to A site (except for initiator methinine), requires an elongation factor and GTP
166
Protein Elongation Process: Step 2
rRNA ("ribozyme") catalyzes peptide bond formation, transfers growing polypeptide to amino acid in A site
167
Protein Elongation Process: Step 3
Ribosome advances 3 nucleotides toward 3' end of mRNA, moving peptidyl tRNA to P site (translocation)
168
Protein Elongation Process
**APE**
* **A** site = incoming **A**minoacyl-tRNA
* **P** site = accommodates growing **P**eptide
* **E** site = holds **E**mpty tRNA as it **E**xits
169
Posttranslational Modifications:
removal of N- or C-terminaal propeptides from zymogen to generate mature protein (e.g. trypsinogen → trypsin
Trimming
170
Posttranslational Modifications:
Covalent Alterations
* phosphorylation
* glycosylation
* hydroxylation
* methylation
* acetylation
* ubiquitination
171
Posttranslational Modifications:
intracellular protein involved in facilitationg and/or maintaining protein folding
Chaperone Protein
172
Cell cycle phases are regulated by \_\_\_\_\_,
* cyclins
* cyclin-dependent kinases (CDKs)
* tumor suppressors
173
The _____ is the shortest phase of the cell cycle and includes \_\_\_\_\_.
M Phase
* Mitosis
* Cytokinesis
174
Mitosis Steps
1. Prophase
2. Prometaphase
3. Metaphase
4. Anaphase
5. Telophase
175
\_\_\_\_\_ occurs when the cytoplasm splits into 2.
Cytokinesis
176
Cell Cycle
177
Cell Cycle Regulation:
* constitutive
* inactive
Cyclin-Dependent Kinases (CDKs)
178
Cell Cycle Regulation:
* regulatory proteins to coordinate cell cycle progression
* phase specific
* activate CDKs
Cyclins
179
Cell Cycle Regulation:
* phosphorylate other proteins to coordinate cell cycle progression
* must be activated and inactivated at appropriate times for the cell cycle to progress
Cyclin-CDK Complexes
180
Cell Cycle Regulation:
* supresses cell division
* mutations can lead to tumors
Tumor Suppressors
181
Tumor Suppression
p53 induces p21 → inhibits CDKs → hypophosphrylation (activation) of Rb → inhibition of G1-S progression
182
Growth factors bind _____ to transition the cell from G1 to S phase.
tyrosine kinase receptors
183
Cell Types:
* remain in G0
* regenerate from stem cells
* neurons, skeletal and cardiac muscle, RBCs
Permanent
184
Cell Types:
* enter G1 from G0 when stimulated
* hepatocytes, lymphocytes, PCT, periosteal cells
Stable (Quiescent)
185
Cell Types:
* never go to G0
* divide rabpidly with a short G1
* most affeced by chemotherapy
* bone marrow, gut epithelium, skin, hair follicles, germ cells
Labile
186
The _____ is the site of synthesis of secretpry ((exported) proteins and of N-linked oligosaccharide addition to many proteins.
Rough Endoplasmic Reticulum
187
\_\_\_\_\_ are RER in neurons which synthesize peptide neurotansmitters for secretion.
Nissl Bodies
188
\_\_\_\_\_ are the site of synthesis of cytosolic and organellar proteins.
Free Ribosomes
189
Mucus-secreting goblet cells of the small intestine and antibody-secreting plasma cells are rich in \_\_\_\_\_.
RER
190
The _____ is the site of steroid synthesis and detoxification of drugs and poisons.
Smooth Endoplasmic Reticulum
191
Liver hepatocytes and steroid hormone-producing cells of the adrenal cortex and gonads are rich in \_\_\_\_\_.
SER
192
Cell Trafficking
193
The _____ is the distribution center for proteins and lipids from the ER to the vesicles and plasma membrane.
Golgi Apparatus
194
The golgi apparatus modifies N-oligosaccharides on \_\_\_\_\_.
Asparagine
195
The golgi apparatus adds O-oligosaccharides on \_\_\_\_\_.
Serine
Threonine
196
The golgi apparatus adds _____ to proteins for trafficking to lysosomes.
mannose-6-phosphate
197
\_\_\_\_\_ are sorting centers for material from outside the cell or from the Golgi, sending it to lysosomes for destruction or back to the membrane/Golgi for further use.
Endosomes
198
\_\_\_\_\_ is an inherited lysosomal storage disorder which causes coarse facial features, gingival hyerplasia, clouded corneas, restricted joint movements, clawhand deformities, kyphoscoliosis and high levels of lysosomal enzymes. It is often fatal in childhood.
Inclusion Cell Disease
(I-Cell DIsease/Mucolipidosis type II)
199
Inclusion Cell Disease Pathogensis
defect in N-acetylglucosaminyl-1-phosphotransferase → failure of the Golgi to phosphorylate mannose residues (↓ mannose-6-phosphate) on glycoproteins → proteins are secreted extracellularly rather than delivered to lysosomes
200
\_\_\_\_\_ is an abundant, cytosolic ribonucleoprotein that traffics proteins from the ribosome to the RER.
Signal Recognition Paticle (SRP)
201
Absent or dysfunctional _____ leads to protein accumulation in the cytosol.
SRP
202
Vesicular Trafficking Proteins:
* Golgi → Golgi (retrograde)
* cis-Golgi → ER
COPI
203
Vesicular Trafficking Proteins:
ER → cis-Golgi (anterograde)
COPII
204
Vesicular Trafficking Proteins:
* trans-Golgi → lysosomes
* plasma membranes → endosomes (receptor -mediated endocytosis)
Clathrin
205
\_\_\_\_\_ are membrane-enclosed organelles involved in :
* β-oxidation of very-long-chain fatty acids (VLCFA)
* α-oxidation
* catabolism of branched-chain fatty acids, amino acids and ethanol
* synthesis of cholesterol, bile acids and plasmalogens (important membrane phospholipid, especially in white matter of brain)
Peroxisomes
206
\_\_\_\_\_ is an autosomal recessive disorder of peroxisome biogenesis due to mutated PEX genes cauzing hypotonia, seizures, hepatomegaly and early death.
Zellweger Syndrome
207
\_\_\_\_\_ is an autosomal recessive disorder of α-oxidation → phytanic acid is not metabolized to pristanic acid causing scaly skin, ataxia, cataracts, night blindness, shortening of the 4th toe, epiphyseal dysplasia.
Refsum Disease
208
Refsum Disease:
Treatment
diet
plasmapheresis
209
\_\_\_\_\_ is an X-linked recessive disorder of β-oxidation → VLCFA buildup in adrenal glands, white matter and testes → adrenal gland crisis, coma and death.
Adrenoleukodystrophy
210
The _____ is a barrel-shaped protein complex that degrades damaged or ubiquitin-tagged proteins.
Proteasome
211
Defects in the _____ have been implicated in some cases of Parkinson Disease.
Ubiquitin-Proteasome System
212
\_\_\_\_\_ is a network of protein fibers within the cytoplasm that supports cell structure, cell and organelle movement and cell division.
Cytoskeletal Elements
213
Types of Filaments:
* muscle contraction
* cytokinesis
Microfilaments
214
Types of Filaments:
* actin
Microfilaments
215
Types of Filaments:
* microvilli
Microfilaments
216
Types of Filaments:
maintains cell structure
Intermediate Filaments
217
Types of Filaments:
vimentin
Intermediate Filaments
218
Types of Filaments:
desmin
Intermediate Filaments
219
Types of Filaments:
cytokeratin
Intermediate Filaments
220
Types of Filaments:
lamins
Intermediate Filaments
221
Types of Filaments:
glial fibrillary acidic protein (GFAP)
Intermediate Filaments
222
Types of Filaments:
neurofilaments
Intermediate Filaments
223
Types of Filaments:
* movement
* cell division
Microtubules
224
Types of Filaments:
cilia
Microtubules
225
Types of Filaments:
flagella
Microtubules
226
Types of Filaments:
mitotic spindle
Microtubules
227
Types of Filaments:
axonal trafficking
Microtubules
228
Types of Filaments:
centrioles
Microtubules
229
\_\_\_\_\_ have a cylindrical outer structure composed of a helical array of polymerized heterodimers of α- and β-tubulin.
Microtubules
230
Each dimer on a microtubule has a _____ bond.
2 GTP
231
\_\_\_\_\_ are incorporated into flagella, cilia and mitotic spindles.
Microtubules
232
Microtubules grow _____ and collapse \_\_\_\_\_.
grow slowly
collapse quickly
233
Microtubule Structure
234
\_\_\_\_\_ transport cellular cargo toward opposite ends of microtubule tracks.
Molecular Motor Proteins
235
Molecular Motor Proteins:
retrograde to microtubule (+ → -)
Dynein
**N**egative end **N**ear **N**ucleus
236
Molecular Motor Proteins:
anterograde to microtubule (- → +)
Kinesin
**P**ositive end **P**oints to **P**eriphery
237
Drugs that act on Microtubules
**M**icrotubules **G**et **C**onstructed **V**ery **P**oorly
* **M**ebendazole (antihelmintic)
* **G**riseofulvin (antifungal)
* **C**olchicine (antigout)
* **V**incristine/**V**inblastine (anticancer)
* **P**aclitaxel (anticancer)
238
Cilia microtubules are arranged as \_\_\_\_\_.
* 9 doublet + 2 singlet
* 9 triplets (basal body)
239
\_\_\_\_\_ is an ATPase that links peripheral 9 doublets and causes bending of cilium by differential sliding of doublets.
Axonemal Dynein
240
\_\_\_\_\_ enable coordinated ciliary movement.
Gap Junctions
241
\_\_\_\_\_ is an autosomal recessive disease which causes immotile cilia due to a dynein arm defect. It causes ↓ fertility due to immotile sperm and dysfunctional fallopian tube cilia (↑ ectopic pregnancy). It also presents with bronchiectasis, recurrent sinusitis, chronic ear infections, conductive hearing loss and situs inversus.
Kartagener Syndrome
(1° Ciliary Dyskinesia)
242
Sodium-Potassium Pump
243
Na+-K+ ATPase is located in the plasma membrane with the ATP site on the \_\_\_\_\_.
cytosolic side
244
For each ATP consumed by Na+-K+ ATPase, _____ go out of the cell and _____ come into the cell.
* 3Na+ out - pump phosphorylated
* 2K+ in - pump dephosphorylated
**Pumpkin** = **pump K+ in**
245
The _____ is an asymmetric lipid bilayer containing cholesterol, phospholipids, sphingolipids, glycolipidsand proteins.
plasma membrane
246
\_\_\_\_\_ inhibits Na+-K+ ATPase by binding to the K+ site.
Ouabain
\*cardiac glycoside
247
\_\_\_\_\_ directly inhibit the Na+-K+ ATPase, which leads to the indirect inhibition of Na+/Ca2+ exchange → ↑ [Ca2+]i → ↑ cardiac contractility.
Digoxin and Digitoxin
\* cardiac glycosides
248
\_\_\_\_\_ is the most abundant protein in the body, is extensively modified by posttranslational modification and organizes and strengthens extracellular matrix.
Collagen
249
Collagen Types
**B**e **S**o **T**otally **C**ool, **R**ead **B**ig **B**ooks.
1. **B**one, **S**kin, **T**endon
2. **C**artilage
3. **R**eticulin, **B**lood vessels
4. **B**asement membrane
250
Collagen Types:
most common (90%)
Type I
251
Collagen Types:
bone (made by osteoblasts)
Type I
\*↓ production in osteogenesis Imperfecta type I
252
Collagen Types:
skin
Type I
253
Collagen Types:
tendon
Type I
254
Collagen Types:
dentin
Type I
255
Collagen Types:
fascia
Type I
256
Collagen Types:
cornea
Type I
257
Collagen Types:
late wound repair
Type I
258
Collagen Types:
cartilage
Type II
Car**TWO**lage
259
Collagen Types:
vitreous body
Type II
260
Collagen Types:
nucleus pulposus
Type II
261
Collagen Types:
reticulin
Type III
262
Collagen Types:
blood vessels
Type III
263
Collagen Types:
uterus
Type III
264
Collagen Types:
fetal tissue
Type III
265
Collagen Types:
granulation tissue
Type III
266
Collagen Types:
deficient in the uncommon, vascular type of Ehlers-Danlos syndrome
Type III
**E**hlers-**D**anlos = **ThreE D**
267
Collagen Types:
basement membrane
Type IV
Type **4** = under the **floor** (basement)
268
Collagen Types:
basal lamina
Type IV
269
Collagen Types:
lens
Type IV
270
Collagen Synthesis and Structure
271
Collagen Synthesis
1. Synthesis
2. Hydroxylation
3. Glycosylation
4. Exocytosis
5. Proteolytic Processing
6. Cross-Linking
272
Collagen synthesis begins with the translation of \_\_\_\_\_.
collagen α chains
(preprocollagen)
\*usually Gly-X-Y
\*X - proline
\*Y - lysine
273
\_\_\_\_\_ content best reflects collagen synthesis.
Glycine
\*collagen is 1/3 glycine
274
During collagen synthesis, _____ redidues are hydroxylated.
proline
lysine
275
Collagen hydroxylation requires \_\_\_\_\_.
Vitamin C
\*deficiency → scurvy
276
During collagen synthesis, _____ are glycosylated.
pro-α-chain hydroxylysine residues
277
During collagen glycosylation, procollagen is formed via \_\_\_\_\_.
hydrogen and disulfide bonds
(triple helix of 3 collagen α chains)
\*problems forming triple helix → osteogenesis imperfecta
278
During collagen synthesis, _____ is exocytosed into the extracellular space.
procollagen
279
During proteolytic processing of collagen, cleavage of disulfide-rich terminal regions of procollagen forms \_\_\_\_\_.
insoluble tropocollagen
\*problems with cleavage → Ehlers-Danlos
280
During collagen cross-linking, staggered tropocollagen molecules are reinforced by _____ to make collagen fibrils.
covalent lysine-hydroxylisine cross-linkage
(by copper-containing lysyl oxidase)
\*problems with cross-linking → Ehler-Danlos, Menkes
281
\_\_\_\_\_ is a genetic bone disorder caused by a variety of gene defeccts (most commonly COL1A1 and COL1A2).
Osteogenesi Imperfecta
(brittle bone disease)
282
The most common form of osteogenesis imperfecta in _____ with ↓ production of \_\_\_\_\_.
autosomal dominant
Type I collagen
283
Osteogenesis Imperfecta Manifestations
Patients cam't **BITE**.
* **B**ones = multiple fractures with minimal trauma
* **I** (eye) = blue sclerae - translucent connective tissue overchoroidal veins
* **T**eeth = tooth abnormalities - opalescent teeth that wear easily due to lack of dentin (dentinogenesis imperfecta)
* **E**ar = hearing loss (abnormal ossicles)
284
Osteogenesis Imperfecta is treated with \_\_\_\_\_.
biphosponates
285
\_\_\_\_\_ is a disease with faulty collagen synthesis causing hyperextensible skin, hypermobile joints and a tendency to bleed (easy bruising).
Ehlers-Danlos Syndrome
286
The most common type of Ehlers-Danlos Syndrome is \_\_\_\_\_.
Hypermobility Type
(joint instability)
287
The classical type of Ehlers-Danlos Syndrome is caused by a mutation in \_\_\_\_\_.
Type V Collagen
(joint and skin)
288
The vascular type of Ehlers-Danlos Syndrome is caused by a deficiency in _____ which affects fragile tissues, vessels, muscles and organs that are prone to rupture.
Type III Procollagen
289
\_\_\_\_\_ disease is an X-linked recessive connective tissue disease caused by impaired copper absorption and transfport due to defective ATP7A (\_\_\_\_\_ protein).
Menkes
290
Menkes disease causes ↓ activity of _____ → defective collagen.
lysyl oxidase
\*copper is a necessary cofactor
291
\_\_\_\_\_ disease causes brittle, "kinky" hair, growth retardation and hypotonia.
Menkes
292
\_\_\_\_\_ is a stretchy protein within skin, lungs, large arteries, elastic ligaments, vocal cords and ligamenta flava.
Elastin
293
Elastin Structure
294
Elastin is rich in \_\_\_\_\_.
nonhydroxylated proline, glycine and lysine residues.
295
Elastin is composed of \_\_\_\_\_.
tropoelastin with fibrillin scaffolding
296
Elastin cross-linking takes place _____ and gives it elastic properties.
extracellularly
297
Elastin is broken down by \_\_\_\_\_.
Elastase
298
Elastase is inhibited by \_\_\_\_\_.
α1-antitrypsin
299
\_\_\_\_\_ deficiency results in unopposed elastase activity which can cause emphysema.
α1-antitrypsin
300
Changes with Aging
* ↓ dermal collagen and elastin
* ↓ synthesis of collagen fibrils
* crosslinking remains normal
301
\_\_\_\_\_ is an autosomal dominant connective tissue disorder affecting skeleton, heart and eyes because of FBN1 gene mutation on chromosome 15.
Marfan Syndrome
302
In Marfan Syndrome, FBN1 gene mutation on chromosome 15 results in defective \_\_\_\_\_, a glycoprotein that forms a sheath around elastin.
fibrillin
303
\_\_\_\_\_ manifests with tall stature, long extremities, pectus carinatum (more specific) or pectus excavatum, hypermobile joints, long tapering fingers and toes (arachnodactyly), cystic medial necrosis of the aorta, aortic incompetence, dissecting aortic aneurysms, floppy mitral valve and subluxation of lenses (upward and temporally).
Marfan Syndrome
304
\_\_\_\_\_ is a molecular biology lab procedure used to amplify a desired fragment of DNA.
Polymerase Chain Reaction
305
Polymerase Chain Reaction
306
Polymerase Chain Reaction
1. Denaturation
2. Annealing
3. Elongation
307
In PCR, DNA is heated to _____ to separate strands.
95°C
308
During the annealing process of PCR, the sample is cooled to \_\_\_\_\_.
55°C
309
During the annealing process of PCR, _____ are added.
* DNA primers
* heat-stable DNA polymerase (Taq)
* deoxynucleotide triphosphates (dNTPs)
310
During the elongation process of PCR, the temperature is increased to \_\_\_\_\_.
72°C
311
During the elongation process of PCR, DNA polymerase attaches _____ to the strand to replicate the sequence after each primer.
dNTPs
312
\_\_\_\_\_ is a genome editing tool derived from bacteria.
CRISPR
313
CRISPR is composed of an endonuclease, \_\_\_\_\_, which cleaves dsDNA and a guide RNA (gRNA) sequence that binds to complementary target DNA sequence.
Cas9
314
CRISPR:
cell DNA repair machinery (nonhomologous end joining) fills in the gap introduced by the system
knock-out
knock-**out** = removing a gene, taking it **out**
315
CRISPR:
a donor DNA can be added to the system to fill the gap
knock-in
knock-**in** = **in**serting a gene.
316
Blotting Procedures
**SN**o**W DR**o**P**
* **S**outhern = **D**NA
* **N**orthern = **R**NA
* **W**estern = **P**rotein
317
Southern Blot
318
Southern Blot Procedure
1. DNA sample is enzymatically cleaved into smaller pieces,which are separated on a gel by electrophoresis, and then transferred to a filter.
2. Filter is exposed to radiolabeled DNA probe that recognizes and anneals to its complementary strand.
3. Resulting double-stranded, labeled piece of DNA is visualized when filter is exposed to film.
319
\_\_\_\_\_ is similar to Southern Blot, except that an RNA sample is electrophoresed. It is useful of studying mRNA levels, which are reflective of gene expression.
Northern Blot
320
In \_\_\_\_\_, a sample protein is separated via gel electrophoresis and transferred to a membrane. The labeled antibody is used to bind to relevant protein.
Western Blot
321
\_\_\_\_\_ identifies DNA-binding proteins (eg. transcription factors) using labeled oligonucleotide probes.
Southwestern Blot
322
\_\_\_\_\_ is a laboratory technique which assesses the size, granularity, and protein expression (immunophenotype) of individual cells in a sample.
Flow Cytometry
323
In \_\_\_\_\_, cells are tagged with antibodies specific to surface or intracellular proteins. Antibodies are then tagged with a unique fluorescent dye. The sample is analyzed one cell at a time by focusing a laser on the cell and measuring light scatter and intensity of fluorescence.
Flow Cytometry
324
\_\_\_\_\_ is a laboratory technique commonly used in workup of hematologic abnormalities (eg. paroxysmal nocturnal hemoglobinuria, fetal RBCs in mother’s blood) and immunodeficiencies (eg. CD4 cell count in HIV).
Flow Cytometry
325
Flow Cytometry data are plotted either as _____ or \_\_\_\_\_.
* histogram (one measure)
* scatter plot (any two measures)
326
Flow Cytometry
327
In \_\_\_\_\_, thousands of nucleic acid sequences are arranged in grids on glass or silicon. DNA or RNA probes are hybridized to the chip, and a scanner detects the relative amounts of complementary binding.
Microarrays
328
\_\_\_\_\_ are used to profile gene expression levels of thousands of genes simultaneously to study certain diseases and treatments. Able to detect single nucleotide polymorphisms (SNPs) and copy number variations (CNVs) for a variety of applications including genotyping, clinical genetic testing, forensic analysis, cancer mutations, and genetic linkage analysis.
Microarrays
329
\_\_\_\_\_ is an immunologic test used to detect the presence of either a specific antigen (eg. HBsAg) or antibody (eg. anti-HBs) in a patient’s blood sample.
Enzyme-Linked Immunosorbent Assay (ELISA)
330
In \_\_\_\_\_, detection involves the use of an antibody linked to an enzyme. Added substrate reacts with enzyme, producing a detectable signal. It can have high sensitivity and specificity, but is less specific than Western blot.
Enzyme-Linked Immunosorbent Assay (ELISA)
331
Direct ELISA tests for the \_\_\_\_\_.
antigen
332
Indirect ELISA tests for the \_\_\_\_\_.
antibody
333
\_\_\_\_\_ is a process in which metaphase chromosomes are stained, ordered, and numbered according to morphology, size, arm-length ratio, and banding pattern.
Karyotyping
334
Karyotyping can be performed on a sample of \_\_\_\_\_.
* blood
* bone marrow
* amniotic fluid
* placental tissue
335
In \_\_\_\_\_, a fluorescent DNA or RNA probe binds to
specific gene site of interest on chromosomes. Used for specific localization of genes and direct
visualization of chromosomal anomalies at the
molecular level.
Fluorescence In Situ Hybridization (FISH)
336
FISH:
no fluorescence on a chromosome compared to fluorescence at the same locus on the second copy of that chromosome
Microdeletion
337
FISH:
fluorescence signal that corresponds to one chromosome is found in a different chromosome
Translocation
338
FISH:
a second copy of a chromosome, resulting in a trisomy or tetrasomy
Duplication
339
\_\_\_\_\_ is the production of a recombinant DNA molecule in a bacterial host.
Molecular Cloning
340
Molecular Cloning
1. Isolate eukaryotic mRNA (post-RNA processing) of interest.
2. Add reserve transcriptase (an RNA-dependent DNA polymerase) to produce complementary DNA (cDNA, lacks introns).
3. Insert cDNA fragments into bacterial plasmids containing antibiotic resistance genes.
4. Transform (insert) recombinant plasmid into bacteria.
5. Surviving bacteria on antibiotic medium produce cloned DNA (copies of cDNA).
341
Transgenic strategies in mice involve \_\_\_\_\_.
* Random insertion of gene into mouse genome
* Targeted insertion or deletion of gene through homologous recombination with mouse gene
342
Gene Expression Modifications:
Random Insertion
Constitutive
343
Gene Expression Modifications:
Targeted Insertion
Conditional
344
\_\_\_\_\_ can inducibly manipulate genes at specific developmental points (eg. to study a gene whose deletion causes embryonic death).
Cre-Lox System
345
In \_\_\_\_\_, dsRNA is synthesized that is complementary to the mRNA sequence of interest. When transfected into human cells, dsRNA separates and promotes degradation of target mRNA, “knocking down” gene expression.
RNA Interference
346
Genetics:
both alleles contribute to the phenotype of the heterozygote
Codominance
347
Genetics:
* blood groups A, B, AB
* α1-antitrypsi deficiency
* HLA groups
Codominance
348
Genetics:
patients with the same genotype have varying phenotypes
Variable Expressivity
349
Genetics:
2 patients with neurofibromatosis type 1 (NF1) may have varying disease severity
Variable Expressivity
350
Genetics:
not all individuals with a mutant genotype show the mutant phenotype
Incomplete Penetrance
% penetrance × probability of inheriting genotype = risk of expressing phenotype.
351
Genetics:
BRCA1 gene mutations do not always result in breast or ovarian cancer
Incomplete Penetrance
352
Genetics:
one gene contributes to multiple phenotypic effects
Pleiotropy
353
Genetics:
untreated phenylketonuria (PKU) manifests with light skin, intellectual disability, and musty body odor
Pleiotropy
354
Genetics:
increased severity or earlier onset of disease in succeeding generations
Anticipation
355
Genetics:
trinucleotide repeat diseases (eg. Huntington disease)
Anticipation
356
Genetics:
if a patient inherits or develops a mutation in a tumor suppressor gene, the complementary allele must be deleted/mutated before cancer develops (not true of oncogenes)
Loss of Heterozygosity
357
Genetics:
* Retinoblastoma and the “two-hit hypothesis”
* Lynch Syndrome (HNPCC)
* Li-Fraumen Syndrome
Loss of Heterozygosity
358
Genetics:
exerts a dominant effect, a heterozygote produces a nonfunctional altered protein that also prevents the normal gene product from functioning
Dominant Negative Mutation
359
Genetics:
mutation of a transcription factor in its allosteric site, nonfunctioning mutant can still bind DNA preventing wild-type transcription factor from binding
Dominant Negative Mutation
360
Genetics:
tendency for certain alleles at 2 linked loci to occur together more or less often than expected by chance, measured in a population, not in a family, and often varies in different populations
Linkage Disequilibrium
361
Genetics:
presence of genetically distinct cell lines in the
same individual
Mosaicism
362
Genetics:
mutation arises from mitotic errors after fertilization and propagates through multiple tissues or organs
Somatic Mosaicism
363
Genetics:
mutation only in egg or sperm cells, if parents and relatives do not have the disease suspect gonadal (or germline) mosaicism
Gonadal Mosaicism
364
\_\_\_\_\_ is due to a mutation affecting G-protein signaling. It presents with unilateral café-au-lait spots with ragged edges, polyostotic fibrous dysplasia (bone is replaced by collagen and fibroblasts), and at least one endocrinopathy (eg. precocious puberty). Lethal if mutation occurs before fertilization (affecting all cells), but survivable in patients with mosaicism.
McCune-Albright Syndrome
365
Genetics:
mutations at different loci can produce a similar phenotype
Locus Heterogeneity
366
Genetics:
albinism
Locus Heterogeneity
367
Genetics:
different mutations in the same locus produce the same phenotype
Allelic Heterogeneity
368
Genetics:
β-thalassemia
Allelic Heterogeneity
369
Genetics:
presence of both normal and mutated mtDNA, resulting in variable expression in mitochondrially inherited disease
Heteroplasmy
370
Genetics:
mtDNA passed from mother to all children
Heteroplasmy
371
Genetics:
offspring receives 2 copies of a chromosome from 1 parent and no copies from the other parent
Uniparental Disomy
372
Heterodisomy (heterozygous) indicates a \_\_\_\_\_.
meiosis I error
Heterod**I**somy = meiosis **I** error
373
Isodisomy (homozygous) indicates a _____ or postzygotic chromosomal duplication of one of a pair of chromosomes, and loss of the other of the original pair.
meiosis II error
**I**sod**I**somy = meiosis **II** error
374
Uniparental disomy (UPD) is \_\_\_\_\_. Most occurrences of uniparental disomy → normal phenotype. Consider UPD in an individual manifesting a recessive disorder when only one parent is a carrier. Examples: Prader Willi and Angelman Syndromes
euploid
(correct number of chromosomes)
375
Genetics:
Prader Willi and Angelman Syndromes
Uniparental Disomy
376
If a population is in Hardy-Weinberg equilibrium and if p and q are the frequencies of separate alleles, then \_\_\_\_\_.
p2 + 2pq + q2 = 1 and p + q = 1, which implies that:
* p2 = frequency of homozygosity for allele A
* q2 = frequency of homozygosity for allele a
* 2pq = frequency of heterozygosity (carrier frequency, if an autosomal recessive disease).
The frequency of an X-linked recessive disease in males = q and in females = q2.
377
Hardy-Weinberg law assumptions include:
* No mutation occurring at the locus
* Natural selection is not occurring
* Completely random mating
* No net migration
378
Genetics:
one gene copy is silenced by methylation, and only the other copy is expressed → parent-of-origin effects
Imprinting
379
\_\_\_\_\_ occurs when maternally derived genes are silenced (imprinted). Disease occurs when the paternal allele is deleted or mutated. Results in hyperphagia, obesity, intellectual disability, hypogonadism, and hypotonia. Associated with a mutation or deletion of chromosome 15 of paternal origin. 25% of cases due to maternal uniparental disomy.
Prader-Willi Syndrome
**P**rader-Willi = **P**aternal
380
\_\_\_\_\_ occurs when paternally derived UBE3A gene is silenced (imprinted). Disease occurs when the maternal allele is deleted or mutated. Results in inappropriate laughter (“happy puppet”), seizures, ataxia, and severe intellectual disability. Associated with mutation or deletion of the UBE3A gene on the maternal copy of chromosome 15. 5% of cases due to paternal uniparental disomy.
Angelman Syndrome
Angel**M**an = **M**aternal
381
Modes of Inheritance
Autosomal Dominant
382
Modes of Inheritance
Autosomal Recessive
383
Modes of Inheritance
X-linked Recessive
384
Modes of Inheritance
X-linked Dominant
385
Modes of Inheritance
Mitochondrial Inheritance
386
Modes of Inheritance:
* often due to defects in structural genes
* many generations, both males and females are affected
* often pleiotropic (multiple apparently unrelated effects) and variably expressive (different between individuals)
* with one affected (heterozygous) parent 1/2 of children are affected.
Autosomal Dominant
387
Modes of Inheritance:
* often due to enzyme deficiencies
* usually seen in only 1 generation
* commonly more severe than dominant disorders
* patients often present in childhood.
* ↑ risk in consanguineous families.
* With 2 carrier (heterozygous) parents, on average: ¼ of children will be affected (homozygous), ½ of children will be carriers, and ¼ of children will be neither affected nor carriers.
Autosomal Recessive
388
Modes of Inheritance:
* sons of heterozygous mothers have a 50% chance of being affected
* no male-to-male transmission
* skips generations
* commonly more severe in males
* females usually must be homozygous to be affected
X-linked Recessive
389
Modes of Inheritance:
* transmitted through both parents
* mothers transmit to 50% of daughters and sons
* fathers transmit to all daughters but no sons
X-linked Dominant
390
Modes of Inheritance:
Hypophosphatemic Rickets
X-linked Dominant
391
Modes of Inheritance:
Fragile X Syndrome
X-linked Dominant
392
Modes of Inheritance:
Alport Syndrome
X-linked Dominant
393
\_\_\_\_\_, formerly known as vitamin D-resistant rickets, is an inherited disorder resulting in ↑ phosphate wasting at the proximal tubule.
Hypophosphatemic Rickets
394
Modes of Inheritance:
* transmitted only through the mother
* all offspring of affected females may show signs of disease
* variable expression in a population or even within a family due to heteroplasmy
Mitochondrial Inheritance
395
Modes of Inheritance:
Mitochondrial Myopathies
Mitochondrial Inheritance
396
Modes of Inheritance:
Leber Hereditary Optic Neuropathy
Mitochondrial Inheritance
397
\_\_\_\_\_ are rare disorders, often presenting with myopathy, lactic acidosis, and CNS disease.
Mitochondrial Myopathies
398
\_\_\_\_\_ is 2° to failure in oxidative phosphorylation. Muscle biopsy often shows “ragged red fibers” (due to accumulation of diseased mitochondria).
MELAS Syndrome
* Mitochondrial Encephalomyopathy
* Lactic Acidosis
* Stroke-like episodes
399
\_\_\_\_\_ causes cell death in optic nerve neurons → subacute bilateral vision loss in teens/young adults, 90% males. It is usually permanent.
Leber Hereditary Optic Neuropathy
400
Modes of Inheritance:
Achondroplasia
Autosomal Dominant
401
Modes of Inheritance:
Familial Adenomatous Polyposis
Autosomal Dominant
402
Modes of Inheritance:
Familial Hypercholesterolemia
Autosomal Dominant
403
Modes of Inheritance:
Hereditary Hemorrhagic Telangiectasia (Osler-Weber-Rendu Syndrome)
Autosomal Dominant
404
Modes of Inheritance:
Hereditary Spherocytosis
Autosomal Dominant
405
Modes of Inheritance:
Huntington Disease
Autosomal Dominant
406
Modes of Inheritance:
Li-Fraumeni Syndrome
Autosomal Dominant
407
Modes of Inheritance:
Marfan Syndrome
Autosomal Dominant
408
Modes of Inheritance:
Multiple Endocrine Neoplasias
Autosomal Dominant
409
Modes of Inheritance:
Myotonic Muscular Dystrophy
Autosomal Dominant
410
Modes of Inheritance:
Neurofibromatosis Type 1
(von Recklinghausen Disease)
Autosomal Dominant
411
Modes of Inheritance:
Neurofibromatosis Type 2
Autosomal Dominant
412
Modes of Inheritance:
Tuberous Sclerosis
Autosomal Dominant
413
Modes of Inheritance:
von Hippel-Lindau Disease
Autosomal Dominant
414
Modes of Inheritance:
Albinism
Autosomal Recessive
415
Modes of Inheritance:
Cystic Fibrosis
Autosomal Recessive
416
Modes of Inheritance:
Friedreich Ataxia
Autosomal Recessive
417
Modes of Inheritance:
Glycogen Storage Diseases
Autosomal Recessive
418
Modes of Inheritance:
Hemochromatosis
Autosomal Recessive
419
Modes of Inheritance:
Kartagener Syndrome
Autosomal Recessive
420
Modes of Inheritance:
Mucopolysaccharidoses
(except Hunter Syndrome)
Autosomal Recessive
421
Modes of Inheritance:
Phenylketonuria
Autosomal Recessive
422
Modes of Inheritance:
Sickle Cell Anemia
Autosomal Recessive
423
Modes of Inheritance:
Sphingolipidoses
(except Fabry Disease)
Autosomal Recessive
424
Modes of Inheritance:
Thalassemias
Autosomal Recessive
425
Modes of Inheritance:
Wilson Disease
Autosomal Recessive
426
\_\_\_\_\_ is an autosomal recessive disease caused by a defect in CFTR gene on chromosome 7, commonly a deletion of Phe508.
Cystic Fibrosis
427
\_\_\_\_\_ is the most common lethal genetic disease in Caucasian population.
Cystic Fibrosis
428
* CFTR encodes an ATP-gated Cl− channel that secretes Cl− in lungs and GI tract, and reabsorbs Cl− in sweat glands.
* Most common mutation: misfolded protein → protein retained in RER and not transported to cell membrane, causing ↓ Cl− (and H2O) secretion; ↑ intracellular Cl− results in compensatory ↑ Na+ reabsorption via epithelial Na+ channels → ↑ H2O reabsorption → abnormally thick mucus secreted into lungs and GI tract.
* ↑ Na+ reabsorption also causes more negative transepithelial potential difference.
Cystic Fibrosis
429
* ↑ Cl− concentration in pilocarpine-induced sweat test is diagnostic.
* Can present with contraction alkalosis and hypokalemia (ECF effects analogous to a patient taking a loop diuretic) because of ECF H2O/Na+ losses and concomitant renal K+/H+ wasting.
* ↑ immunoreactive trypsinogen (newborn screening).
Cystic Fibrosis
430
* Recurrent pulmonary infections (eg. S aureus [early infancy], P aeruginosa [adolescence]), chronic bronchitis and bronchiectasis → reticulonodular pattern on CXR, opacification of sinuses.
* Pancreatic insufficiency, malabsorption with steatorrhea, fat-soluble vitamin deficiencies (A, D, E, K), biliary cirrhosis, liver disease.
* Meconium ileus in newborns.
* Infertility in men (absence of vas deferens, spermatogenesis may be unaffected) and subfertility in women (amenorrhea, abnormally thick cervical mucus).
* Nasal polyps, clubbing of nails.
Cystic Fibrosis
431
Cystic Fibrosis Treatment
* **Multifactorial:** chest physiotherapy, _albuterol_, _aerosolized dornase alfa (DNase)_, and _hypertonic saline_ facilitate mucus clearance. _Azithromycin_ used as anti-inflammatory agent. _Ibuprofen_ slows disease progression.
* In patients with **Phe508 deletion:** combination of _lumacaftor_ (corrects misfolded proteins and improves their transport to cell surface) and _ivacaftor_ (opens Cl– channels → improved chloride transport).
432
X-linked Recessive Disorders
**O**blivious **F**emale **W**ill **O**ften **G**ive **H**er **B**oys **H**er x-**L**inked **D**isorders
* **O**rnithine Transcarbamylase Deficiency
* **F**abry Disease
* **W**iskott-Aldrich Syndrome
* **O**cular Albinism
* **G**6PD Deficiency
* **H**unter Syndrome
* **B**ruton Agammaglobulinemia
* **H**emophilia A and B
* **L**esch-Nyhan Syndrome
* **D**uchenne (and Becker) Muscular Dystrophy
433
In \_\_\_\_\_, female carriers are variably affected depending on the pattern of inactivation of the X chromosome carrying the mutant vs. normal gene.
X-Inactivation
(Lyonization)
434
Females with _____ are more likely to have an X-linked recessive disorder.
Turner Syndrome (45,XO)
435
\_\_\_\_\_ is an X-linked disorder typically due to **frameshift** or nonsense mutations → truncated or absent dystrophin protein → progressive myofiber damage.
Duchenne Muscular Dystrophy
436
In Duchenne Muscular Dystrophy, weakness begins in the _____ and progresses _____ leading to a _____ gait.
pelvic girdle muscles
superiorly
waddling
437
In Duchenne Muscular Dystrophy, pseudohypertrophy of calf muscles is due to \_\_\_\_\_.
fibrofatty replacement of muscle
438
The onset of Duchenne Muscular Dystrophy is \_\_\_\_\_.
before 5 y.o.
439
In Duchenne Muscular Dystrophy, the most common cause of death is \_\_\_\_\_.
dilated cardiomyopathy
440
\_\_\_\_\_ is deomonstrated when a patient uses upper extremities to help stand up.
Gower Sign
441
\_\_\_\_\_ is the largest protein-coding human gene → ↑ chance of spontaneous mutation.
Dystrophin Gene
442
\_\_\_\_\_ helps anchor muscle fibers, primarily in skeletal and cardiac muscle. It connects the intracellular cytoskeleton (actin) to the transmembrane proteins α- and β-dystroglycan, which are connected to the extracellular matrix (ECM).
Dystrophin
443
\_\_\_\_\_ presents with ↑ CK and aldolase; genetic testing confirms the diagnosis.
Duchenne Muscular Dystrophy
444
Duchenne Muscular Dystrophy
445
\_\_\_\_\_ is an X-linked disorder typically due to nonframeshift deletions in dystrophin gene
(partially functional instead of truncated).
Becker Muscular Dystrophy
\*less severe than Duchenne
446
Th onset of Becker Muscular Dystrophyis in \_\_\_\_\_.
adolescence
early adulthood
447
\_\_\_\_\_ is an autosomal dominant disease. CTG trinucleotide repeat expansion in the DMPK gene → abnormal expression of myotonin protein kinase → myotonia, muscle wasting, cataracts, testicular atrophy, frontal balding, arrhythmia.
Myotonic Type 1 Muscular Dystrophy
**CTG** trinucleotide repeat
* **C**ataracts
* **T**oupee (early balding in men)
* **G**onadal atrophy
448
\_\_\_\_\_ is a sporadic disorder seen almost exclusively in girls (affected males die in utero or shortly after birth). Most cases are caused by de novo mutation of MECP2 on X chromosome.
Rett Syndrome
449
The symptoms of Rett Syndrome usually appear between \_\_\_\_\_.
1-4 y.o.
450
Rett Syndrome is characterized by \_\_\_\_\_.
* regression (**Rett**urn) in motor, verbal, and cognitive abilities
* ataxia
* seizures
* growth failure
* stereotyped handwringing
451
\_\_\_\_\_ is an X-linked Dominant disease. Trinucleotide repeat in FMR1 gene → hypermethylation → ↓ expression.
Fragile X Syndrome
452
\_\_\_\_\_ is the most common cause of inherited intellectual disability and 2nd most common cause of genetically associated mental deficiency (after Down syndrome).
Fragile X Syndrome
453
\_\_\_\_\_ presents with post-pubertal macroorchidism (enlarged testes), long face with a large jaw, large everted ears, autism, mitral valve prolapse.
Fragile X Syndrome
454
The trinucleotide repeat expansionin Fragile X Syndrome [(CGG)n] occurs during \_\_\_\_\_.
oogenesis
455
Trinucleotide repeat expansion diseases may show _____ (disease severity ↑ and age of onset ↓ in successive generations).
genetic anticipation
456
Trinucleotide Repeat Expansion Diseases
**Try** (**tri**nucleotide) **hunting** for **my** **fragile** cage**free** eggs (**X**).
* **Hunting**ton Disease
* **My**otonic Dystrophy
* **Fragile X** Syndrome
* **Frie**dreich Ataxia
457
Huntington Disease Trinucleotide Repeat
**CAG**
**C**audate has ↓ **A**Ch and **G**ABA
458
Myotonic Gystrophy Trinucleotide Repeat
**CTG**
* **C**ataracts
* **T**oupee (early balding in men)
* **G**onadal atrophy
459
Fragile X Syndrome Trinucleotide Repeat
**CGG**
* **C**hin (protruding)
* **G**iant **G**onads
460
Friedreich Ataxia Trinucleotide Repeat
**GAA**
Ataxic **GAA**it
461
\_\_\_\_\_ presents with intellectual disability, flat facies, prominent epicanthal folds, single palmar crease, gap between 1st 2 toes, duodenal atresia, Hirschsprung disease, congenital heart disease (eg. atrioventricular septal defect), Brushfield spots, early-onset Alzheimer disease (chromosome 21 codes for amyloid precursor protein) and ↑ risk of ALL and AML.
**D**own **S**yndrome
**D**rinking age (**21**)
| (Trisomy **21**)
462
95% of Down Syndrome cases are due to \_\_\_\_\_.
meiotic nondisjunction
\*↑ with advanced maternal age; from 1:1500 in women \< 20 to 1:25 in women \> 45 years old
463
4% of Down Syndrome cases are due to \_\_\_\_\_, most typically between \_\_\_\_\_.
unbalanced Robertsonian translocation
chromosomes 14 and 21
464
Only 1% of Down Syndrome cases are due to \_\_\_\_\_.
postfertilization mitotic error
465
The incidence of Down Syndrome is \_\_\_\_\_.
1:700
466
\_\_\_\_\_ is the most common viable chromosomal disorder and most common cause of genetic intellectual disability.
Down Syndrome
467
First-trimester ultrasound of Down Syndrome commonly shows \_\_\_\_\_.
↑ nuchal translucency
hypoplastic nasal bone
468
Down Syndrome Findings
The **5 A**’s of Down Syndrome:
* **A**dvanced maternal age
* **A**tresia (duodenal)
* **A**trioventricular septal defect
* **A**lzheimer disease (early onset)
* **A**ML/**A**LL
469
\_\_\_\_\_ presents with prominent occiput, rocker-bottom feet, intellectual disability, nondisjunction, clenched fists (with overlapping fingers), low-set ears, micrognathia (small jaw), congenital heart disease. Death usually occurs by age 1.
**E**dwards Syndrome
**E**lection age (**18**)
| (Trisomy **18**)
470
The incidence of Edwards Syndrome is \_\_\_\_\_.
1:8000
471
\_\_\_\_\_ is the 2nd most common autosomal trisomy resulting in live birth.
Edwards Syndrome
472
Edwards Syndrome Findings
**PRINCE** Edward
* **P**rominent occiput
* **R**ocker-bottom feet
* **I**ntellectual disability
* **N**ondisjunction
* **C**lenched fists (with overlapping fingers)
* low-set **E**ars,
473
\_\_\_\_\_ presents with severe intellectual disability, rocker-bottom feet, microphthalmia, microcephaly, cleft lip/palate, holoprosencephaly, polydactyly, cutis aplasia, congenital heart disease, polycystic kidney disease. Death usually occurs by age 1.
**P**atau Syndrome
**P**uberty (**13**)
| (Trisomy **13**)
474
The incidence of Patau Syndrome is \_\_\_\_\_.
1:15,000
475
Patau Syndrome Findings
The 5 P’s of Patau Syndrome:
* cleft li**P**/**P**alate
* holo**P**rosencephaly
* **P**olydactyly
* cutis a**P**lasia
* **P**olycystic kidney disease
476
Trisomies
477
Genetic Disorders:
Chromosome 3
von Hippel-Lindau Disease
Renal Cell Carcinoma
478
Genetic Disorders:
Chromosome 4
ADPKD (PKD2)
Achondroplasia
Huntington Disease
479
Genetic Disorders:
Chromosome 5
Cri-du-chat Syndrome
Familial Adenomatous Polyposis
480
Genetic Disorders:
Chromosome 6
Hemochromatosis (HFE)
481
Genetic Disorders:
Chromosome 7
Williams Syndrome
Cystic Fibrosis
482
Genetic Disorders:
Chromosome 9
Friedreich Ataxia
Tuberous Sclerosis (TSC1)
483
Genetic Disorders:
Chromosome 11
Wilms Tumor
β-globin Gene Defects
(eg. sickle cell disease, β-thalassemia)
MEN1
484
Genetic Disorders:
Chromosome 13
Patau Syndrome
Wilson Disease
Retinoblastoma (RB1)
BRCA2
485
Genetic Disorders:
Chromosome 15
Prader-Willi Syndrome
Angelman Syndrome
Marfan Syndrome
486
Genetic Disorders:
Chromosome 16
ADPKD (PKD1)
α-globin Gene Defects
(eg. α-thalassemia)
Tuberous Sclerosis (TSC2)
487
Genetic Disorders:
Chromosome 17
Neurofibromatosis Type 1
BRCA1
p53
488
Genetic Disorders:
Chromosome 18
Edwards Syndrome
489
Genetic Disorders:
Chromosome 21
Down Syndrome
490
Genetic Disorders:
Chromosome 22
Neurofibromatosis Type 2
DiGeorge Syndrome (22q11)
491
Genetic Disorders:
X Chromosome
Fragile X Syndrome
X-linked Agammaglobulinemia
Klinefelter Syndrome (XXY)
492
\_\_\_\_\_ is a chromosomal translocation that commonly involves chromosome pairs 13, 14, 15, 21, and 22. It is one of the most common types of translocation. It occurs when the long arms of 2 acrocentric chromosomes (chromosomes with centromeres near their ends) fuse at the centromere and the 2 short arms are lost.
Robertsonian Translocation
493
Unbalanced _____ can result in miscarriage, stillbirth, and chromosomal imbalance (eg. Down Syndrome, Patau Syndrome).
Robertsonian Translocation
494
\_\_\_\_\_ is caused by the congenital deletion on the short arm of chromosome 5 (46,XX or XY, 5p−).
Cri-du-chat Syndrome
495
\_\_\_\_\_ presents with microcephaly, moderate to severe intellectual disability, high-pitched crying/ meowing, epicanthal folds, cardiac abnormalities (VSD).
Cri-du-chat Syndrome
496
\_\_\_\_\_ is caused by the congenital microdeletion of the long arm of chromosome 7 (deleted region includes elastin gene).
Williams Syndrome
497
\_\_\_\_\_ presents with distinctive “elfin” facies, intellectual disability, hypercalcemia (↑ sensitivity to vitamin D), well-developed verbal skills, extreme friendliness with strangers, cardiovascular problems (eg. supravalvular aortic stenosis, renal artery stenosis).
Williams Syndrome
498
22q11 Deletion Syndromes
DiGeorge Syndrome
Velocardiofacial Syndrome
499
22q11 Deletion Syndrome Findings
**CATCH-22**
microdeletion at chromosome **22**q11 → **C**left palate, **A**bnormal facies, **T**hymic aplasia → T-cell deficiency, **C**ardiac defects, and **H**ypocalcemia 2° to parathyroid aplasia
500
22q11 Deletion Syndromes result in the aberrant development of the \_\_\_\_\_.
3rd and 4th branchial (pharyngeal) pouches
501
22q11 Deletion Syndromes:
thymic, parathyroid, and cardiac defects
DiGeorge Syndrome
502
22q11 Deletion Syndromes:
palate, facial, and cardiac defects
Velocardiofacial Syndrome
503
Fat Soluble Vitamins
A, D, E, K
504
Absorption of fat soluble vitamins is dependent on the \_\_\_\_\_.
gut and pancreas
505
Toxicity more common in fat-soluble
vitamins than for water-soluble vitamins because \_\_\_\_\_.
fat-soluble vitamins accumulate in fat
506
Malabsorption syndromes with steatorrhea (eg. cystic fibrosis and celiac disease) or mineral oil intake can cause \_\_\_\_\_.
fat-soluble vitamin deficiencies
507
Water Soluble Vitamins
* B1 (thiamine: TPP)
* B2 (riboflavin: FAD, FMN)
* B3 (niacin: NAD+)
* B5 (pantothenic acid: CoA)
* B6 (pyridoxine: PLP)
* B7 (biotin)
* B9 (folate)
* B12 (cobalamin)
* C (ascorbic acid)
508
B Vitamins
**T**he **R**egular **N**ight **P**ub **P**rovided **B**eer **F**or **C**oby.
* B1 (**T**hiamine: TPP)
* B2 (**R**iboflavin: FAD, FMN)
* B3 (**N**iacin: NAD+)
* B5 (**P**antothenic acid: CoA)
* B6 (**P**yridoxine: PLP)
* B7 (**B**iotin)
* B9 (**F**olate)
* B12 (**C**obalamin)
509
Water soluble vitamins all wash out easily from body except \_\_\_\_\_.
B9 and B12
510
B9 and B12 are stored in the \_\_\_\_\_.
liver (~3-4 years)
511
B-complex deficiencies often result in \_\_\_\_\_.
* dermatitis
* glossitis
* diarrhea
512
Vitamin A is also called \_\_\_\_\_.
Retinol
513
\_\_\_\_\_ is an antioxidant; a constituent of visual pigments (retinal); essential for normal differentiation of epithelial cells into specialized tissue (pancreatic cells, mucus-secreting cells); prevents squamous metaplasia; used to treat measles and acute promyelocytic leukemia (APL).
Vitamin A
514
Vitamin A is found in \_\_\_\_\_.
liver
leafy vegetables
515
\_\_\_\_\_ is used to treat severe cystic acne.
oral isotretinoin
516
\_\_\_\_\_ is used to treat acute promyelocytic leukemia.
all-trans retinoic acid
517
\_\_\_\_\_ causes night blindness (nyctalopia), dry scaly skin (xerosis cutis), corneal degeneration (keratomalacia), Bitot spots (foamy appearance) on conjunctiva and immunosuppression.
Vitamin A Deficiency
518
\_\_\_\_\_ causes nausea, vomiting, vertigo, and blurred vision.
Acute Vitamin A Toxicity
519
\_\_\_\_\_ causes alopecia, dry skin (eg. scaliness), hepatic toxicity and enlargement, arthralgias, and pseudotumor cerebri.
Chronic Vitamin A Toxicity
520
A ⊝ pregnancy test and two forms of contraception are required before isotretinoin (vitamin A derivative) is prescribed because it is \_\_\_\_\_.
teratogenic
(cleft palate, cardiac abnormalities)
521
Vitamin B1 is also called \_\_\_\_\_.
Thiamine
522
In thiamine pyrophosphate (TPP), vitamin B3 is a cofactor for several dehydrogenase enzyme reactions:
**ATP**
* **α**-ketoglutarate dehydrogenase (TCA cycle)
* **T**ransketolase (HMP shunt)
* **P**yruvate dehydrogenase (links glycolysis to TCA cycle)
* Branched-chain ketoacid dehydrogenase
523
\_\_\_\_\_ causes impaired glucose breakdown → ATP depletion worsened by glucose infusion; highly aerobic tissues (eg. brain, heart) are affected first.
Vitamin B1 Deficiency
(Beriberi)
**B**er**1B**er**1**
524
Diagnosis of Vitamin B1 Deficiency is made by _____ following vitamin B1 administration.
↑ in RBC transketolase activity
525
\_\_\_\_\_ causes confusion, ophthalmoplegia, ataxia, confabulation, personality change, memory loss (permanent) and damage to medial dorsal
nucleus of thalamus and mammillary bodies.
Wernicke-Korsakoff Syndrome
Triad:
* confusion
* ophthalmoplegia
* ataxia
526
In alcoholic or malnourished patients, give thiamine before dextrose to ↓ risk of precipitating \_\_\_\_\_.
Wernicke Encephalopathy
527
\_\_\_\_\_ causes polyneuropathy and symmetrical
muscle wasting.
Dry beriberi
528
\_\_\_\_\_ causes high-output cardiac failure (dilated cardiomyopathy), edema.
Wet Beriberi
529
Vitamin B2 is also called \_\_\_\_\_.
Riboflavin
530
\_\_\_\_\_ is a component of flavins FAD and FMN, used as cofactors in redox reactions, eg. the succinate dehydrogenase reaction in the TCA cycle.
Vitamin B2
**F**AD and **F**MN are derived from ribo**F**lavin (B**2** ≈ **2** ATP).
531
\_\_\_\_\_ causes cheilosis (inflammation of lips, scaling and fissures at the corners of the mouth), corneal vascularization.
Vitamin B2 Deficiency
The **2 C**’s of B**2:**
* **C**heilosis
* **C**orneal vascularization
532
Vitamin B3 is also called \_\_\_\_\_.
Niacin
533
\_\_\_\_\_ is a constituent of NAD+, NADP+ (used in redox reactions). Derived from tryptophan. Synthesis requires vitamins B2 and B6. Used to treat dyslipidemia; lowers levels of VLDL and raises levels of HDL.
Vitamin B3
**N**AD derived from **N**iacin (B**3** ≈ **3** ATP).
534
Synthesis of Vitamin B3 requires \_\_\_\_\_.
Vitamins B2 and B6
535
Vitamin B3 is derived from \_\_\_\_\_.
Tryptophan
536
\_\_\_\_\_ causes glossitis and severe deficiency leads to pellagra, which can also be caused by Hartnup disease, malignant carcinoid syndrome (↑ tryptophan metabolism), and isoniazid (↓ vitamin B6).
Vitamin B3 Deficiency
(Pellagra)
537
Symptoms of Pellagra
The **3 D**’s of B**3**:
* **D**iarrhea
* **D**ementia (also hallucinations)
* **D**ermatitis (C3/C4 dermatome circumferential “broad collar” rash [Casal necklace], hyperpigmentation of sunexposed limbs).
538
\_\_\_\_\_ is an autosomal recessive disease which causes deficiency of neutral amino acid (eg. tryptophan) transporters in proximal renal tubular cells and on enterocytes → neutral aminoaciduria and ↓ absorption from the gut → ↓ tryptophan for conversion to niacin → pellagra-like symptoms. Treat with high protein diet and nicotinic acid.
Hartnup Disease
539
\_\_\_\_\_ causes facial flushing (induced by prostaglandin, not histamine; can be avoided by taking aspirin), hyperglycemia, hyperuricemia.
Vitamin B3 Toxicity
(Podagra)
540
Vitamin B5 is also called \_\_\_\_\_.
Pantothenic Acid
541
\_\_\_\_\_ is an Eessential component of coenzyme A (CoA, a cofactor for acyl transfers) and fatty acid synthase.
Vitamin B5
542
\_\_\_\_\_ causes dermatitis, enteritis, alopecia, adrenal insufficiency.
Vitamin B5 Deficiency
543
Vitamin B6 is also called \_\_\_\_\_.
Pyridoxine
544
\_\_\_\_\_ is converted to pyridoxal phosphate (PLP), a cofactor used in transamination (eg. ALT and AST), decarboxylation reactions, glycogen phosphorylase, synthesis of cystathionine, heme, niacin, histamine, and neurotransmitters including serotonin, epinephrine, norepinephrine (NE), dopamine, and GABA.
Vitamin B6
545
\_\_\_\_\_ causes convulsions, hyperirritability, peripheral neuropathy (deficiency inducible by isoniazid and oral contraceptives), sideroblastic anemias (due to impaired hemoglobin synthesis and iron excess).
Vitamin B6 Deficiency
546
Vitamin B7 is also called \_\_\_\_\_.
Biotin
547
Vitamin B7 is a cofactor for carboxylation enzymes (which add a 1-carbon group):
* Pyruvate carboxylase: pyruvate (3C) → oxaloacetate (4C)
* Acetyl-CoA carboxylase: acetyl-CoA (2C) → malonyl-CoA (3C)
* Propionyl-CoA carboxylase: propionyl-CoA (3C) → methylmalonyl-CoA (4C)
548
\_\_\_\_\_ presents with dermatitis, enteritis and alopecia. It is caused by antibiotic use or excessive ingestion of raw egg whites (avidin).
Vitamin B7 Deficiency
549
Vitamin B9 is also called \_\_\_\_\_.
Folate
550
\_\_\_\_\_ is converted to tetrahydrofolic acid (THF), a coenzyme for 1-carbon transfer/methylation reactions. Important for the synthesis of nitrogenous bases in DNA and RNA.
Vitamin B9
551
Vitamin B9 is found in \_\_\_\_\_.
leafy green vegetables
**Fol**ate from **Fol**iage
552
Vitamin B9 is absorbed in the \_\_\_\_\_.
jejunum
553
A small reserve pool of Vitamin B9 is stored primarily in the \_\_\_\_\_.
liver
554
\_\_\_\_\_ causes macrocytic, megaloblastic anemia; hypersegmented polymorphonuclear cells (PMNs); glossitis; no neurologic symptoms. Labs: ↑ homocysteine, normal methylmalonic acid levels. Seen in alcoholism and pregnancy.
Vitamin B9 Deficiency
555
Vitamin B9 Deficiency can be caused by drugs such as \_\_\_\_\_.
Phenytoin
Sulfonamides
Methotrexate
556
Supplemental maternal folic acid is given at least _____ prior to conception and during early pregnancy to ↓ risk of neural tube defects.
1 month
557
Vitamin B12 is also called \_\_\_\_\_.
Cobalamin
558
\_\_\_\_\_ is a cofactor for methionine synthase (transfers CH3 groups as methylcobalamin) and methylmalonyl CoA mutase. Important for DNA synthesis.
Vitamin B12
559
Vitamin B12 is found in \_\_\_\_\_.
animal products
560
Vitamin B12 is synthesized only by \_\_\_\_\_.
microorganisms
561
Vitamin B12 has a very large reserve pool (several years) stored primarily in the \_\_\_\_\_.
liver
562
\_\_\_\_\_ causes macrocytic, megaloblastic anemia; hypersegmented PMNs; paresthesias and subacute combined degeneration (degeneration of dorsal columns, lateral corticospinal tracts, and spinocerebellar tracts) due to abnormal myelin. Associated with ↑ serum homocysteine and methylmalonic acid levels, along with 2° folate deficiency. Prolonged deficiency → irreversible nerve damage.
Vitamin B12 Deficiency
563
Vitamin B12 Deficiency is caused by \_\_\_\_\_.
* malabsorption (eg. sprue, enteritis, Diphyllobothrium latum, achlorhydria, bacterial overgrowth, alcohol excess)
* lack of intrinsic factor (eg. pernicious anemia, gastric bypass surgery)
* absence of terminal ileum (surgical resection, eg. for Crohn disease)
* insufficient intake (eg. veganism)
564
The presence of anti-intrinsic factor antibodies is diagnostic for \_\_\_\_\_.
Pernicious Anemia
565
Folate supplementation can mask the hematologic symptoms of B12 deficiency, but not the \_\_\_\_\_.
neurologic symptoms
566
Vitamin B6 and B12 Processes
567
Vitamin C is also called \_\_\_\_\_.
ascorbic acid
568
\_\_\_\_\_ is an antioxidant that also facilitates iron absorption by reducing it to Fe2+ state. Necessary for hydroxylation of proline and lysine in collagen synthesis. Necessary for dopamine β-hydroxylase, which converts dopamine to NE.
Vitamin C
569
Vitamin C is found in \_\_\_\_\_.
fruits and vegetables
570
\_\_\_\_\_ is an ancillary treatment for methemoglobinemia by reducing Fe3+ to Fe2+.
Vitamin C
571
\_\_\_\_\_ causes swollen gums, bruising, petechiae, hemarthrosis, anemia, poor wound healing, perifollicular and subperiosteal hemorrhages, “corkscrew” hair and weakened immune response.
Vitamin C Deficiency
(Scurvy)
Vitamin **C** deficiency causes s**C**urvy due to a
**C**ollagen synthesis defect.
572
\_\_\_\_\_ causes nausea, vomiting, diarrhea, fatigue, calcium oxalate nephrolithiasis. Can ↑ iron toxicity in predisposed individuals by increasing dietary iron absorption (ie. can worsen hereditary hemochromatosis or transfusion-related iron overload).
Vitamin C Toxicity
573
Vitamin D2 (ergocalciferol) comes from ingestion of \_\_\_\_\_.
* plants
* fungi
* yeasts
574
Vitamin D3 (cholecalciferol) comes from \_\_\_\_\_.
* exposure of skin (stratum basale) to sun
* fish
* milk
* plants
575
Vitamin D2 is also called \_\_\_\_\_.
Ergocalciferol
576
Vitamin D3 is also called \_\_\_\_\_.
Cholecalciferol
577
Vitamin D2 and D3 are converted to their stirage form _____ in the \_\_\_\_\_.
25-OH D3
liver
578
Vitamin D2 and D3 are converted to their active form, \_\_\_\_\_, in the \_\_\_\_\_.
1,25-(OH)2 D3 (calcitriol)
kidney
579
Functions of Vitamin D
* ↑ intestinal absorption of Ca2+ and PO43
* ↑ bone mineralization at low levels
* ↑ bone resorption at higher levels
580
At low levels of Vitamin D, there is \_\_\_\_\_.
↑ bone mineralization
581
At high levels of Vitamin D, there is \_\_\_\_\_.
↑ bone resorption
582
Vitamin D Regulation
* ↑ PTH, ↓ Ca2+, ↓ PO43– → ↑ 1,25-(OH)2D3 production
* 1,25-(OH)2D3 feedback inhibits its own production.
* ↑ PTH → ↑ Ca2+ reabsorption and ↓ PO43– reabsorption in the kidney.
583
Vitamin D Deficiency causes _____ in children (deformity, such as genu varum “bow legs”).
Rickets
584
Vitamin D Deficiency causes _____ in adults (bone pain and muscle weakness).
Osteomalacia
585
Vitamin D Deficiency causes \_\_\_\_\_.
* Rickets in children (deformity, such as genu varum “bow legs”)
* Osteomalacia in adults (bone pain and muscle weakness)
* Hypocalcemic Tetany
586
Vitamin D Deficiency is caused by \_\_\_\_\_.
* malabsorption
* ↓ sun exposure
* poor diet
* chronic kidney disease
587
Vitamin D Deficiency is exacerbated by \_\_\_\_\_.
* pigmented skin
* premature birth
588
Oral Vitamin D is given to _____ infants.
breastfed
589
\_\_\_\_\_ causes hypercalcemia, hypercalciuria, loss of appetite and stupor and is seen in granulomatous disease (↑ activation by epithelioid macrophages).
Vitamin D Toxicity
590
Vitamin E includes \_\_\_\_\_.
* tocopherol
* tocotrienol
591
\_\_\_\_\_ is an antioxidant (protects RBCs and membranes from free radical damage). High-dose supplementation may alter metabolism of vitamin K → enhanced anticoagulant effects of warfarin.
Vitamin E
592
\_\_\_\_\_ causes hemolytic anemia, acanthocytosis, muscle weakness, posterior column and spinocerebellar tract demyelination.
Vitamin E Deficiency
593
The neurologic presentation of _____ may appear similar to vitamin B12 deficiency, but without megaloblastic anemia, hypersegmented neutrophils or ↑ serum methylmalonic acid levels.
Vitamin E Deficiency
594
Excess vitamin E ↑ risk of _____ in infants.
enterocolitis
595
Vitamin K includes \_\_\_\_\_.
* phytomenadione
* phylloquinone
* phytonadione
* menaquinone
596
\_\_\_\_\_ is activated by epoxide reductase to the reduced form, which is a cofactor for the γ-carboxylation of glutamic acid residues on various proteins required for blood clotting. Synthesized by intestinal flora.
Vitamin K
597
Vitamin K is necessary for the maturation of\_\_\_\_\_.
* clotting factors II, VII, IX, X (1972)
* proteins C and S
598
\_\_\_\_\_ inhibits vitamin K-dependent synthesis of clotting factors and proteins.
Warfarin
599
\_\_\_\_\_ causes neonatal hemorrhage with ↑ PT and ↑ aPTT but normal bleeding time (neonates have sterile intestines and are unable to synthesize \_\_\_\_\_). Can also occur after prolonged use of broad-spectrum antibiotics.
Vitamin K Deficiency
600
\_\_\_\_\_ is not in breast milk therefore neonates are given _____ injection at birth to prevent hemorrhagic disease of the newborn.
Vitamin K
601
\_\_\_\_\_ is a mineral essential for the activity of 100+ enzymes. Important in the formation of _____ (transcription factor motif).
Zinc
Zinc Fingers
602
\_\_\_\_\_ causes delayed wound healing, suppressed immunity, hypogonadism, ↓ adult hair (axillary, facial, pubic), dysgeusia, anosmia, acrodermatitis enteropathica. May predispose to alcoholic cirrhosis.
Zinc Deficiency
603
\_\_\_\_\_ is protein malnutrition resulting in skin lesions, edema due to ↓ plasma oncotic pressure, liver malfunction (fatty change due to ↓ apolipoprotein synthesis). Clinical picture is small child with swollen abdomen.
Kwashiorkor
604
Kwashiorkor Findings
Kwashiorkor results from protein deficient **MEALS**:
* **M**alnutrition
* **E**dema
* **A**nemia
* **L**iver (fatty)
* **S**kin lesions (eg, hyperkeratosis, dyspigmentation)
605
\_\_\_\_\_ is malnutrition not causing edema. Diet is deficient in calories but no nutrients are entirely absent.
Marasmus
**M**arasmus results in **M**uscle wasting.
606
Ethanol Metabolism
607
\_\_\_\_\_ inhibits alcohol dehydrogenase and is an antidote for overdoses of methanol or ethylene glycol.
Fomepizole
**FOME**pizole = **F**or **O**verdoses of **M**ethanol or **E**thylene glycol
608
\_\_\_\_\_ inhibits acetaldehyde dehydrogenase (acetaldehyde accumulates, contributing to hangover symptoms), discouraging drinking.
Disulfiram
609
\_\_\_\_\_ is the limiting reagent in ethanol metabolism.
NAD+
610
Alcohol dehydrogenase operates via \_\_\_\_\_.
zero-order kinetics
611
Ethanol metabolism ↑ NADH/NAD+ ratio in
liver, causing:
* Pyruvate → lactate (lactic acidosis)
* Oxaloacetate → malate (prevents gluconeogenesis → fasting hypoglycemia)
* Dihydroxyacetone phosphate → glycerol-3‑phosphate (combines with fatty acids to make triglycerides → hepatosteatosis)
612
\_\_\_\_\_ disfavors TCA production of NADH → ↑ utilization of acetyl-CoA for ketogenesis (→ ketoacidosis) and lipogenesis (→ hepatosteatosis).
↑ NADH/NAD+ ratio
613
Metabolism Sites:
fatty acid oxidation (β-oxidation)
Mitochondria
614
Metabolism Sites:
acetyl-CoA production
Mitochondria
615
Metabolism Sites:
TCA cycle
Mitochondria
616
Metabolism Sites:
oxidative phosphorylation
Mitochondria
617
Metabolism Sites:
ketogenesis
Mitochondria
618
Metabolism Sites:
glycolysis
Cytoplasm
619
Metabolism Sites:
HMP shunt
Cytoplasm
620
Metabolism Sites:
synthesis of steroids (SER)
Cytoplasm
621
Metabolism Sites:
synthesis of proteins (ribosomes, RER)
Cytoplasm
622
Metabolism Sites:
synthesis of fatty acids
Cytoplasm
623
Metabolism Sites:
synthesis of cholesterol
Cytoplasm
624
Metabolism Sites:
synthesis of nucleotides
Cytoplasm
625
\_\_\_\_\_ are processes which occur in both the mitochondria and the cytoplasm.
**HUG**s take **tw**o (ie, both).
* **H**eme Synthesis
* **U**rea Cycle
* **G**luconeogenesis.
626
Enzymes:
catalyzes transfer of a phosphate group from a high energy molecule (usually ATP) to a substrate (eg. phosphofructo\_\_\_\_\_)
Kinase
627
Enzymes:
adds inorganic phosphate onto substrate without using ATP (eg. glycogen \_\_\_\_\_)
Phosphorylase
628
Enzymes:
removes phosphate group from substrate (eg. fructose-1,6-bis\_\_\_\_\_)
Phosphatase
629
Enzymes:
catalyzes oxidation-reduction reactions (eg. pyruvate \_\_\_\_\_)
Dehydrogenase
630
Enzymes:
adds hydroxyl group (−OH) onto substrate (eg. tyrosine \_\_\_\_\_)
Hydroxylase
631
Enzymes:
transfers CO2 groups with the help of biotin (eg. pyruvate \_\_\_\_\_)
Carboxylase
632
Enzymes:
relocates a functional group within a molecule (eg. vitamin B12-dependent methylmalonyl-CoA \_\_\_\_\_)
Mutase
633
Enzymes:
joins two molecules together using a source of energy (eg. ATP, acetyl CoA, nucleotide sugar)
Synthase/Synthetase
634
Glycolysis:
Rate-Determining Enzyme
Phosphofructokinase-1 (PFK-1)
635
Glycolysis:
Regulators
* AMP ⊕, fructose-2,6-bisphosphate ⊕
* ATP ⊝, citrate ⊝
636
Gluconeogenesis:
Rate-Determining Enzyme
Fructose-1,6-bisphosphatase
637
Gluconeogenesis:
Regulators
* Citrate ⊕
* AMP ⊝, fructose-2,6-bisphosphate ⊝
638
TCA Cycle:
Rate-Determining Enzyme
Isocitrate Dehydrogenase
639
TCA Cycle:
Regulators
* ADP ⊕
* ATP ⊝, NADH ⊝
640
Glycogenesis:
Rate-Determining Enzyme
Glycogen Synthase
641
Glycogenesis:
Regulators
* Glucose-6-phosphate ⊕, insulin ⊕, cortisol ⊕
* Epinephrine ⊝, glucagon ⊝
642
Glycogenolysis:
Rate-Determining Enzyme
Glycogen Phosphorylase
643
Glycogenolysis:
Regulators
* Epinephrine ⊕, glucagon ⊕, AMP ⊕
* Glucose-6-phosphate ⊝, insulin ⊝, ATP ⊝
644
HMP Shunt:
Rate-Determining Enzyme
Glucose-6-Phosphate Dehydrogenase (G6PD)
645
HMP Shunt:
Regulators
* NADP+ ⊕
* NADPH ⊝
646
De novo Pyrimidine Synthesis:
Rate-Determining Enzyme
Carbamoyl Phosphate Synthetase II
647
De novo Pyrimidine Synthesis:
Regulators
* ATP ⊕, PRPP ⊕
* UTP ⊝
648
De novo Purine Synthesis:
Rate-Determining Enzyme
Glutamine-phosphoribosylpyrophosphate (PRPP) Amidotransferase
649
De novo Purine Synthesis:
Regulators
AMP ⊝, inosine monophosphate (IMP) ⊝, GMP ⊝
650
Urea Cycle:
Rate-Determining Enzyme
Carbamoyl Phosphate Synthetase I
651
Urea Cycle:
Regulators
N-acetylglutamate ⊕
652
Fatty Acid Synthesis:
Rate-Determining Enzyme
Acetyl-CoA carboxylase (ACC)
653
Fatty Acid Synthesis:
Regulators
* Insulin ⊕, citrate ⊕
* Glucagon ⊝, palmitoyl-CoA ⊝
654
Fatty Acid Oxidation:
Rate-Determining Enzyme
Carnitine Acyltransferase I
655
Fatty Acid Oxidation:
Regulators
Malonyl-CoA ⊝
656
Ketogenesis:
Rate-Determining Enzyme
HMG-CoA Synthase
657
Cholesterol Synthesis:
Rate-Determining Enzyme
HMG-CoA Reductase
658
Cholesterol Synthesis:
Regulators
* Insulin ⊕, thyroxine ⊕
* Glucagon ⊝, cholesterol ⊝
659
Biochemical Pathways
660
Aerobic metabolism of one glucose molecule produces _____ via malate-aspartate shuttle (heart and liver).
32 net ATP
661
Aerobic metabolism of one glucose molecule produces _____ via glycerol-3-phosphate shuttle (muscle).
30 net ATP
662
Anaerobic glycolysis produces _____ per glucose molecule.
2 net ATP
663
\_\_\_\_\_ can be coupled to energetically unfavorable reactions.
ATP hydrolysis
664
Arsenic causes glycolysis to produce \_\_\_\_\_.
zero net ATP
665
Activated Carriers:
Phosphoryl groups
ATP
666
Activated Carriers:
Electrons
NADH
NADPH
FADH2
667
Activated Carriers:
Acyl groups
CoA
lipoamide
668
Activated Carriers:
CO2
Biotin
669
Activated Carriers:
1-carbon units
Tetrahydrofolates
670
Activated Carriers:
CH3 groups
S-adenosylmethionine (SAM)
671
Activated Carriers:
Aldehydes
TPP
672
Universal Electron Acceptors
* NAD+
* NADP+
* FAD+
673
Nicotinamides from Vitamin B3
* NAD+
* NADP+
674
Flavin Nucleotides from Vitamin B2
FAD+
675
NAD+ is generally used in _____ processes to carry reducing equivalents away as NADH.
catabolic
676
NADPH is used in _____ processes (eg, steroid and fatty acid synthesis) as a supply of reducing equivalents.
anabolic
677
NADPH is a product of the \_\_\_\_\_.
HMP shunt
678
NADPH is used in \_\_\_\_\_.
* Anabolic processes
* Respiratory burst
* Cytochrome P-450 system
* Glutathione reductase
679
Phosphorylation of glucose to yield glucose-6-phosphate is catalyzed by _____ in the liver and _____ in other tissues.
Glucokinase - liver
Hexokinase - other tissues
680
\_\_\_\_\_ sequesters glucose in tissues, where it is used even when glucose concentrations are low.
Hexokinase
681
At high glucose concentrations, _____ helps to store glucose in liver.
Glucokinase
682
Glucose Phosphorylation:
* found in most tissues except liver and pancreatic β cells
* Km - Lower (↑ affinity)
* Vmax - Lower (↓ capacity)
* not induced by insulin
* feedback is inhibited by glucose-6-phosphate
Hexokinase
683
Glucose Phosphorylation:
* found in the liver and β cells of pancreas
* Km - Higher (↓ affinity)
* Vmax - Higher (↑ capacity)
* induced by insulin
* feedback is inhibited by glucose-6-phosphate
Glucokinase
684
Net Glycolysis (cytoplasm)
Glucose + 2 Pi + 2 ADP + 2 NAD+ → 2 pyruvate + 2 ATP + 2 NADH + 2 H+ + 2 H2O
685
Glycolysis Regulation:
Require ATP
686
Glycolysis Regulation:
Produce ATP
687
Regulation by Fructose-2,6-Bisphosphate
688
\_\_\_\_\_ is a mitochondrial enzyme complex linking glycolysis and TCA cycle. Differentially regulated in fed/fasting states (active in fed state).
Pyruvate Dehydrogenase Complex
689
Pyruvate Dehydrogenase Complex Reaction
pyruvate + NAD+ + CoA → acetyl-CoA + CO2 + NADH
690
The Pyruvate Dehydrogenase Complex contains 3 enzymes that require 5 cofactors:
**T**he **L**ovely **C**o-enzymes **F**or **N**erds
1. **T**hiamine pyrophosphate (B1)
2. **L**ipoic acid
3. **C**oA (B5, pantothenic acid)
4. **F**AD (B2, riboflavin)
5. **N**AD+ (B3, niacin)
691
The Pyruvate Dehydrogenase Complex is activated by:
* ↑ NAD+/NADH ratio
* ↑ ADP
* ↑ Ca2+
692
\_\_\_\_\_ inhibits lipoic acid. _____ poisoning clinical findings: imagine a vampire (pigmentary skin changes, skin cancer), vomiting and having diarrhea, running away from a cutie (QT prolongation) with garlic breath.
Arsenic
693
\_\_\_\_\_ is an X-linked disease that causes a buildup of pyruvate that gets shunted to lactate (via LDH) and alanine (via ALT).
Pyruvate Dehydrogenase Complex Deficiency
694
\_\_\_\_\_ causes neurologic defects, lactic acidosis, ↑ serum alanine starting in infancy.
Pyruvate Dehydrogenase Complex Deficiency
695
Pyruvate Dehydrogenase Complex Deficiency is treated with \_\_\_\_\_.
↑ intake of ketogenic nutrients (eg, high fat content or ↑ lysine and leucine).
696
Pyruvate Metabolism
1. Alanine aminotransferase (B6): alanine carries amino groups to the liver from muscle
2. Pyruvate carboxylase (biotin): oxaloacetate can replenish TCA cycle or be used in gluconeogenesis
3. Pyruvate dehydrogenase (B1, B2, B3, B5, lipoic acid): transition from glycolysis to the TCA cycle
4. Lactic acid dehydrogenase (B3): end of anaerobic glycolysis (major pathway in RBCs, WBCs, kidney medulla, lens, testes, and cornea)
697
TCA Cycle (Krebs Cycle)
Pyruvate → acetyl-CoA produces 1 NADH, 1 CO2
**C**itrate **I**s **K**rebs’ **S**tarting **S**ubstrate **F**or **M**aking **O**xaloacetate.
698
The TCA cycle produces \_\_\_\_\_.
3 NADH, 1 FADH2, 2 CO2, 1 GTP per acetyl-CoA = 10 ATP/acetyl-CoA (2× everything per glucose)
699
TCA Cycle reactions occur in the \_\_\_\_\_.
mitochondria
700
α-ketoglutarate dehydrogenase complex requires the same cofactors as the pyruvate dehydrogenase complex:
B1, B2, B3, B5, lipoic acid
701
Electron Transport Chain
702
NADH electrons from glycolysis enter mitochondria via the \_\_\_\_\_.
* malate-aspartate shuttle
* glycerol-3- phosphate shuttle
703
FADH2 electrons are transferred to _____ (at a lower energy level than NADH)
Complex II
704
The passage of electrons results in the formation of a proton gradient that, coupled to \_\_\_\_\_, drives the production of ATP.
Oxidative Phosphorylation
705
ATP produced via ATP Sythase
1 NADH → 2.5 ATP
1 FADH2 → 1.5 ATP
706
\_\_\_\_\_ directly inhibit electron transport, causing a ↓ proton gradient and block of ATP synthesis.
Electron Transport Inhibitors
707
Electron Transport Inhibitors:
Complex I
Rotenone
Roten**one**: complex **one** inhibitor
708
Electron Transport Inhibitors:
Complex III
Antimycin A
“An-**3**-mycin” A: complex **3** inhibitor.
709
Electron Transport Inhibitors:
Complex IV
* Cyanide
* Carbon monoxide
* Azide
The **-ides** (**4 letters**) inhibit complex **IV**.
710
\_\_\_\_\_ directly inhibit mitochondrial ATP synthase, causing an ↑ proton gradient. No ATP is produced because electron transport stops.
ATP Synthase Inhibitors
711
Oligomycin is an _____ inhibitor.
ATP Synthase
712
\_\_\_\_\_ ↑ permeability of membrane, causing a ↓ proton gradient and ↑ O2 consumption. ATP synthesis stops, but electron transport continues. Produces heat.
Uncoupling Agents
713
Uncoupling Agents
* 2,4-Dinitrophenol (used illicitly for weight loss)
* Aspirin (fevers often occur after aspirin overdose)
* Thermogenin in brown fat (has more mitochondria than white fat)
714
Gluconeogenesis:
Irreversible Enzymes
**P**athway **P**roduces **F**resh **G**lucose
* **P**yruvate Carboxylase
* **P**hosphoenolpyruvate Carboxykinase
* **F**ructose-1,6-bisphosphatase
* **G**lucose-6-phosphatase
715
Gluconeogenesis:
* in mitochondria
* pyruvate → oxaloacetate
* requires biotin and ATP
* activated by acetyl-CoA
Pyruvate Carboxylase
716
Gluconeogenesis:
* in cytosol
* oxaloacetate → phosphoenolpyruvate
* requires GTP
Phosphoenolpyruvate Carboxykinase
717
Gluconeogenesis:
* in cytosol
* fructose-1,6-bisphosphate → fructose-6-phosphate
* citrate ⊕, AMP ⊝, fructose 2,6-bisphosphate ⊝
Fructose-1,6-bisphosphatase
718
Gluconeogenesis:
* iIn ER
* glucose-6-phosphate → glucose
Glucose-6-phosphatase
719
\_\_\_\_\_ occurs primarily in liver (also in the kidney and intestinal epithelium); serves to maintain euglycemia during fasting.
Gluconeogenesis
720
Muscle cannot participate in gluconeogenesis because it lacks \_\_\_\_\_.
Glucose-6-phosphatase
721
Odd-chain fatty acids yield _____ during metabolism, which can enter the TCA cycle (as succinyl-CoA), undergo gluconeogenesis, and serve as a glucose source.
1 propionyl-CoA
722
Even-chain fatty acids cannot produce new glucose, since they yield only _____ equivalents.
acetyl-CoA
723
\_\_\_\_\_ provides a source of NADPH from abundantly available glucose-6-P (NADPH is required for reductive reactions, eg, glutathione reduction inside RBCs, fatty acid and cholesterol biosynthesis).
HMP Shunt
(Pentose Phosphate Pathway)
724
\_\_\_\_\_ yields ribose for nucleotide synthesis and has two distinct phases (oxidative and nonoxidative), both of which occur in the cytoplasm. No ATP is used or produced.
HMP Shunt
(Pentose Phosphate Pathway)
725
The HMP Shunt is found in \_\_\_\_\_.
* lactating mammary glands
* liver
* adrenal cortex
* RBCs
\*sites of fatty acid or steroid synthesis
726
HMP Shunt
| (Pentose Phosphate Pathway)
727
\_\_\_\_\_ is necessary to keep glutathione reduced, which in turn detoxifies free radicals and peroxides.
NADPH
728
In \_\_\_\_\_, ↓ NADPH in RBCs leads to hemolytic anemia due to poor RBC defense against oxidizing agents (eg, fava beans, sulfonamides, nitrofurantoin, primaquine/chloroquine, antituberculosis drugs). Infection (most common cause) can also precipitate hemolysis; inflammatory response produces free radicals that diffuse into RBCs, causing oxidative damage.
Glucose-6-Phosphate Dehydrogenase Deficiency
729
\_\_\_\_\_ is an X-linked recessive disorder; most common human enzyme deficiency; more prevalent among African Americans. ↑ malarial resistance.
Glucose-6-Phosphate Dehydrogenase Deficiency
730
Glucose-6-Phosphate Dehydrogenase
731
\_\_\_\_\_ are denatured globin chains that precipitate within RBCs due to oxidative stress.
Heinz Bodies
732
\_\_\_\_\_ result from the phagocytic removal of Heinz bodies by splenic macrophages.
Bite Cells
**Bite** into some **Heinz** ketchup.
733
\_\_\_\_\_ is an autosomal recessive disease which involves a defect in fructokinase. It's a benign, asymptomatic condition, since fructose is not trapped in cells. Hexokinase becomes 1° pathway for converting fructose to fructose-6-phosphate.
Essential Fructosuria
734
\_\_\_\_\_ presents with fructose in the blood and urine. Disorders of fructose metabolism cause milder symptoms than analogous disorders of galactose metabolism.
Essential Fructosuria
735
\_\_\_\_\_ is an autosomal recessive disease which causes a hereditary deficiency of aldolase B. Fructose-1-phosphate accumulates, causing a ↓ in available phosphate, which results in inhibition of glycogenolysis and gluconeogenesis. Hypoglycemia, jaundice, cirrhosis and vomiting present following consumption of fruit, juice, or honey. Urine dipstick will be ⊝ (tests for glucose only); reducing sugar can be detected in the urine (nonspecific test for inborn errors of carbohydrate metabolism).
Hereditary Fructose Intolerance
**F**ructose is to **A**ldolase **B** as **G**alactose is to **U**ridyl**T**ransferase (**FAB GUT**).
736
Hereditary Fructose Intolerance is treated with \_\_\_\_\_.
↓ intake of both fructose and sucrose (glucose + fructose)
737
Fructose Metabolism
738
\_\_\_\_\_ is an autosomal recessive condition where galactitol accumulates if galactose is present in diet. It is a relatively mild condition where galactose appears in blood (galactosemia) and urine (galactosuria). May present as infantile cataracts. failure to track objects or to develop a social smile.
Galactokinase Deficiency
739
\_\_\_\_\_ is an autosomal recessive disease which causes the absence of galactose-1-phosphate uridyltransferase. Damage is caused by accumulation of toxic substances (including galactitol, which accumulates in the lens of the eye). Symptoms develop when infant begins feeding (lactose present in breast milk and routine formula) and include failure to thrive, jaundice, hepatomegaly, infantile cataracts, intellectual disability.
Classic Galactosemia
**F**ructose is to **A**ldolase **B** as **G**alactose is to **U**ridyl**T**ransferase (**FAB GUT**).
740
Classic Galactosemia can predispose neonates to _____ sepsis.
E. coli
741
Classic Galactosemia is treated with \_\_\_\_\_.
exclusion galactose and lactose (galactose + glucose) from diet
742
Galactose Metabolism
743
The more serious cases of galactosemia lead to \_\_\_\_\_.
PO43− depletion
744
An alternative method of trapping glucose in the cell is to convert it to its alcohol counterpart, \_\_\_\_\_, via aldose reductase.
Sorbitol
745
Some tissues then convert sorbitol to fructose using \_\_\_\_\_; tissues with an insufficient amount/activity of this enzyme are at risk of intracellular sorbitol accumulation, causing osmotic damage (eg, cataracts, retinopathy, and peripheral neuropathy seen with chronic hyperglycemia in diabetes).
Sorbitol Dehydrogenase
746
High blood levels of galactose also result in conversion to the osmotically active galactitol via \_\_\_\_\_.
Aldose Reductase
747
\_\_\_\_\_ have both aldose reductase and sorbitol dehydrogenase.
They **LOS**e **sorbitol**.
* **L**iver
* **O**varies
* **S**eminal vesicles
748
\_\_\_\_\_ has primarily aldose reductase while \_\_\_\_\_, \_\_\_\_\_, _____ have only aldose reductase.
**L**u**RKS**
* **L**ens
* **R**etina
* **K**idneys
* **S**chwann cells
749
Sorbitol Metabolism
750
\_\_\_\_\_functions on the intestinal brush border to digest lactose (in milk and milk products) into glucose and galactose.
Lactase
751
Lactase Deficiency:
* age-dependent decline after childhood (absence of lactase-persistent allele)
* common in people of Asian, African, or Native American descent
Primary Lactase deficiency
752
Lactase Deficiency:
loss of intestinal brush border due to gastroenteritis (eg, rotavirus), autoimmune disease, etc.
Secondary Lactase Deficiency
753
\_\_\_\_\_ presents with bloating, cramps, flatulence, and osmotic diarrhea. Stool demonstrates ↓ pH and breath shows ↑ hydrogen content with lactose hydrogen breath test. Intestinal biopsy reveals normal mucosa in patients with hereditary lactose intolerance.
Lactase Deficiency
754
Lactase Deficiency is treated with \_\_\_\_\_.
* avoidance of dairy products
* lactase pills
* lactose-free milk
755
Only _____ are found in proteins.
L-amino acids
756
Essential Amino Acids
**PVT TIM H**a**LL**
* **P**henylalanine
* **V**aline
* **T**yrosine
* **T**hreonine
* **I**soleucine
* **M**ethionine
* **H**istidine
* **L**eucine
* **L**ysine
757
Glucogenic Amino Acids
I **met his val**entine, she is so **sweet** (**gluco**genic).
* **Met**hionine
* **His**tidine
* **Val**ine
758
Glucogenic/Ketogenic Amino Acids
* Isoleucine
* Phenylalanine
* Threonine
* Tyrosine
759
Ketogenic Amino Acids
The on**L**y pure**L**y ketogenic amino acids.
* **L**eucine
* **L**ysine
760
Acidic amino acids (aspartic acid, glutamic acid) are _____ charged at body pH.
negatively charged
761
Basic Amino Acids
**His lys** (lies) **ar**e **basic**.
* **His**tidine
* **Lys**ine
* **Ar**ginine
762
\_\_\_\_\_ is the most basic amino acid.
Arginine
763
Histidine has _____ at body pH.
no charge
764
\_\_\_\_\_ are amino acids required during periods of growth.
* Arginine
* Histidine
765
\_\_\_\_\_ are ↑ in histones which bind negatively charged DNA.
* Arginine
* Lysine
766
\_\_\_\_\_ results in the formation of common metabolites (eg, pyruvate, acetyl-CoA), which serve as metabolic fuels. Excess nitrogen generated by this process is converted to urea and excreted by the kidneys.
Amino Acid Catabolism
767
Urea Cycle
**O**rdinarily, **C**areless **C**rappers **A**re **A**lso **F**rivolous **A**bout **U**rination.
768
Transport of Ammonia by Alanine
769
\_\_\_\_\_ can be acquired (eg, liver disease) or hereditary (eg, urea cycle enzyme deficiencies). Excess NH3 depletes glutamate (GABA) in the CNS and α-ketoglutarate → inhibition of TCA cycle. It is treated with protein limitation in the diet.
Hyperammonemia
770
\_\_\_\_\_ may be given to ↓ ammonia levels.
* Lactulose to acidify the GI tract and trap NH4+ for excretion.
* Antibiotics (eg, rifaximin, neomycin) to ↓ colonic ammoniagenic bacteria.
* Benzoate, phenylacetate, or phenylbutyrate react with glycine or glutamine, forming products that are renally excreted.
771
\_\_\_\_\_ accumulation causes flapping tremor (asterixis), slurring of speech, somnolence, vomiting, cerebral edema, blurring of vision.
Ammonia
772
\_\_\_\_\_ is the most common urea cycle disorder. X-linked recessive (vs other urea cycle enzyme deficiencies, which are autosomal recessive). Interferes with the body’s ability to eliminate ammonia. Often evident in the first few days of life, but may present later. Excess carbamoyl phosphate is converted to orotic acid (part of the pyrimidine synthesis pathway).
Ornithine Transcarbamylase Deficiency
773
\_\_\_\_\_ presents with ↑ orotic acid in blood and urine, ↓ BUN, symptoms of hyperammonemia. No megaloblastic anemia (vs orotic aciduria).
Ornithine Transcarbamylase Deficiency
774
Amino Acid Derivatives
775
Catecholamine Synthesis/Tyrosine Catabolism
776
\_\_\_\_\_ is due to ↓ phenylalanine hydroxylase or ↓ tetrahydrobiopterin (BH4) cofactor (malignant PKU). Tyrosine becomes essential. ↑ phenylalanine → excess phenyl ketones in urine.
Phenylketonuria
777
\_\_\_\_\_ is an autosomal recessive disease which causes intellectual disability, growth retardation, seizures, fair complexion, eczema, musty body odor.
Phenylketonuria
778
Phenylketonuria is treated with \_\_\_\_\_.
* ↓ phenylalanine and ↑ tyrosine in diet
* tetrahydrobiopterin supplementation
779
The incidence of phenylketonuria is \_\_\_\_\_.
1:10,000
780
\_\_\_\_\_ - lack of proper dietary therapy during pregnancy. Findings in infant: microcephaly, intellectual disability, growth retardation, congenital heart defects.
Maternal PKU
781
Phenylketonuria screening occurs _____ after birth (normal at birth because of maternal enzyme during fetal life).
2–3 days
782
Phenyl Ketones
* Phenylacetate
* Phenyllactate
* Phenylpyruvate
783
Phenylketonuria presents with musty body odor due to \_\_\_\_\_.
disorder of aromatic amino acid metabolism
784
PKU patients must avoid the artificial sweetener \_\_\_\_\_, which contains phenylalanine.
Aspartame
785
\_\_\_\_\_ is an autosomal recessive disease where there is blocked degradation of branched amino acids (Isoleucine, Leucine, Valine) due to ↓ branched-chain α-ketoacid dehydrogenase (B1). Causes ↑ α-ketoacids in the blood, especially those of leucine. Causes severe CNS defects, intellectual disability, and death.
Maple Syrup Urine Disease
**I** **L**ove **V**ermont **maple syrup** from maple trees (with **B1**ranches).
786
\_\_\_\_\_ presents with vomiting, poor feeding and urine that smells like maple syrup/burnt sugar.
Maple Syrup Urine Disease
787
Maple Syrup Urine Disease is treated with \_\_\_\_\_.
* restriction of isoleucine, leucine, valine in diet
* thiamine supplementation.
788
\_\_\_\_\_ is an autosomal recessive congenital deficiency of homogentisate oxidase in the degradative pathway of tyrosine to fumarate → pigment-forming homogentisic acid accumulates in tissue. Usually benign.
Alkaptonuria
789
\_\_\_\_\_ presents with bluish-black connective tissue, ear cartilage, and sclerae (ochronosis); urine turns black on prolonged exposure to air. May have debilitating arthralgias (homogentisic acid toxic to cartilage).
Alkaptonuria
790
Homocystinuria Types
* Cystathionine synthase deficiency (treatment: ↓ methionine, ↑ cysteine, ↑ B6, B12, and folate in diet)
* ↓ affinity of cystathionine synthase for pyridoxal phosphate (treatment: ↑↑ B6 and ↑ cysteine in diet)
* Methionine synthase (homocysteine methyltransferase) deficiency (treatment: ↑ methionine in diet)
\*all autosomal recessive
791
Homocystinuria Findings
**HOMOCY**stinuria:
* ↑↑ **H**omocysteine in urine
* **O**steoporosis
* **M**arfanoid habitus,
* **O**cular changes (_downward_ and _inward_ lens subluxation)
* **C**ardiovascular effects (thrombosis and atherosclerosis → stroke and MI)
* k**Y**phosis
* intellectual disability
792
Homocysteine Metabolism
793
\_\_\_\_\_ is an autosomal recessive hereditary defect of renal PCT and intestinal amino acid transporter that prevents reabsorption of Cystine, Ornithine, Lysine, and Arginine Excess cystine in the urine can lead to recurrent precipitation of hexagonal cystine stones.
Cystinuria
**COLA**
* **C**ystine
* **O**rnithine
* **L**ysine
* **A**rginine
794
The incidence of Cystinuria is \_\_\_\_\_.
1:7000
795
\_\_\_\_\_ is diagnostic for Cystinuria.
Urinary Cyanide-Nitroprusside Test
796
Cystinuria is treated with \_\_\_\_\_.
* urinary alkalinization (eg, potassium citrate, acetazolamide) and chelating agents (eg, penicillamine) ↑ solubility of cystine stones
* good hydration
797
Cystine is made of 2 cysteines connected by a \_\_\_\_\_.
disulfide bond
798
Glycogen Regulation by Insulin and Glucagon/Epinephrine
799
Glycogen branches have \_\_\_\_\_.
α-(1,6) bonds
800
Glycogen linkages have \_\_\_\_\_.
α-(1,4) bonds
801
Glycogen Metabolism in Skeletal Muscle
Glycogen undergoes glycogenolysis → glucose-1-phosphate → glucose-6-phosphate, which is rapidly metabolized during exercise.
802
Glycogen Metabolism in Hepatocytes
* Glycogen is stored and undergoes glycogenolysis to maintain blood sugar at appropriate levels.
* Glycogen phosphorylase ④ liberates glucose-1-phosphate residues off branched glycogen until 4 glucose units remain on a branch.
* Then 4-α-d glucanotransferase (debranching enzyme ⑤) moves 3 of the 4 glucose units from the branch to the linkage.
* Then α-1,6-glucosidase (debranching enzyme ⑥) cleaves off the last residue, liberating glucose.
* “Limit dextrin” refers to the one to four residues remaining on a branch after glycogen phosphorylase has already shortened it.
803
At least 15 types of _____ have been identified, all resulting in abnormal glycogen metabolism and an accumulation of glycogen within cells.
Glycogen Storage Diseases
804
\_\_\_\_\_ identifies glycogen and is useful in identifying glycogen storage diseases.
Periodic Acid–Schiff Stain
805
Glycogen Storage Diseases
**V**ery **P**oor **C**arbohydrate **M**etabolism
* **V**on Gierke disease (type I)
* **P**ompe disease (type II)
* **C**ori disease (type III)
* **M**cArdle disease (type V)
\*autosomal recessive.
806
Glycogen Storage Diseases:
* severe fasting hypoglycemia
* ↑↑ glycogen in liver and kidneys
* ↑ blood lactate
* ↑ triglycerides
* ↑ uric acid (gout)
* hepatomegaly
* renomegaly
* liver does not regulate blood glucose
Von Gierke disease (type I)
Von **G**ierke = **G**lycogen, **G**out
807
Glycogen Storage Diseases:
deficient in Von Gierke disease (type I)
Glucose-6-phosphatase
Von **G**ierke = **G**lucose-6-phosphatase
808
Glycogen Storage Diseases:
* oral glucose/cornstarch should be given frequently
* fructose and galactose should be avoided
Von Gierke disease (type I)
809
Glycogen Storage Diseases:
impaired gluconeogenesis and glycogenolysis
Von Gierke disease (type I)
810
Glycogen Storage Diseases:
* cardiomegaly
* hypertrophic
* cardiomyopathy
* hypotonia
* exercise intolerance
* systemic findings lead to early death
Pompe disease (type II)
**Pompe** trashes the **Pump**
(heart, liver, and muscle)
811
Glycogen Storage Diseases:
deficient in Pompe disease (type II)
Lysosomal acid α-1,4-glucosidase with α-1,6-glucosidase activity (acid maltase)
**P**om**P**e trashes the **P**um**P** (**1,4**)
812
Glycogen Storage Diseases:
* milder form of von Gierke (type I) with normal blood lactate levels
* accumulation of limit dextrin–like structures in cytosol
Cori disease (type III)
813
Glycogen Storage Diseases:
deficient in Cori disease (type III)
Debranching enzyme (α-1,6-glucosidase)
814
Glycogen Storage Diseases:
gluconeogenesis is intact
Cori disease (type III)
815
Glycogen Storage Diseases:
* ↑ glycogen in muscle, but muscle cannot break it down → painful muscle cramps
* myoglobinuria (red urine) with strenuous exercise
* arrhythmia from electrolyte abnormalities
* second-wind phenomenon noted during exercise due to ↑ muscular blood flow
McArdle disease (type V)
**M**cArdle = **M**uscle, **M**yoglobinuria
816
Glycogen Storage Diseases:
* deficient in McArdle disease (type V)
* hallmark is a flat venous lactate curve with normal rise in ammonia levels during exercise
Skeletal muscle glycogen phosphorylase (Myophosphorylase)
**M**cArdle = **M**yophosphorylase
817
Glycogen Storage Diseases:
blood glucose levels typically unaffected
McArdle disease (type V)
818
Lysosomal Storage Diseases
Sphingolipidoses
* Tay-Sachs disease
* Fabry disease
* Metachromatic Leukodystrophy
* Krabbe disease
* Niemann-Pick disease
Mucopolysaccharidoses
* Hurler syndrome
* Hunter syndrome
819
Sphingolipidoses:
* autosomal recessive
* progressive neurodegeneration,
* developmental delay
* “cherry-red” spot on macula
* lysosomes with onion skin
* no hepatosplenomegaly (vs Niemann-Pick)
Tay-Sachs disease
820
Sphingolipidoses:
deficient in Tay-Sachs disease
Hexosaminidase A ①
T**A**y-Sa**X** = He**X**osaminidase **A**
821
Sphingolipidoses:
accumulates in Tay-Sachs disease
GM2 ganglioside
822
Sphingolipidoses:
* X-linked recessive
* Early: triad of episodic peripheral neuropathy, angiokeratomas, hypohidrosis
* Late: progressive renal failure, cardiovascular disease
Fabry disease
823
Sphingolipidoses:
deficient in Fabry disease
α-galactosidase A ②
824
Sphingolipidoses:
accumulates in Fabry disease
Ceramide Trihexoside
825
Sphingolipidoses:
* autosomal recessive
* central and peripheral demyelination with ataxia
* dementia
Metachromatic Leukodystrophy
826
Sphingolipidoses:
deficient in Metachromatic Leukodystrophy
Arylsulfatase A ③
827
Sphingolipidoses:
accumulates in Metachromatic Leukodystrophy
Cerebroside Sulfate
828
Sphingolipidoses:
* autosomal recessive
* peripheral neuropathy
* destruction of oligodendrocytes
* developmental delay
* optic atrophy
* globoid cells
Krabbe disease
829
Sphingolipidoses:
deficient in Krabbe disease
Galactocerebrosidase ④
830
Sphingolipidoses:
accumulates in Krabbe disease
* Galactocerebroside
* Psychosine
831
Sphingolipidoses:
* autosomal recessive
* most common
* hepatosplenomegaly
* pancytopenia
* osteoporosis
* avascular necrosis of femur
* bone crises
* Gaucher cells (lipid-laden macrophages resembling crumpled tissue paper)
Gaucher disease
832
Sphingolipidoses:
deficient in Gaucher disease
Glucocerebrosidase (β-glucosidase) ⑤
833
Sphingolipidoses:
accumulates in Gaucher disease
Glucocerebroside
834
Sphingolipidoses:
* autosomal recessive
* progressive neurodegeneration
* hepatosplenomegaly
* foam cells (lipid-laden macrophages)
* “cherry-red” spot on macula
Niemann-Pick disease
835
Sphingolipidoses:
deficient in Niemann-Pick disease
Sphingomyelinase ⑥
**No man picks** (**Niemann-Pick**) his nose with his **sphing**er (**sphing**omyelinase).
836
Sphingolipidoses:
accumulates in Niemann-Pick disease
Sphingomyelin
**No man picks** (**Niemann-Pick**) his nose with his **sphing**er (**sphing**omyelin).
837
Ther is ↑ incidence of Tay-Sachs, Niemann-Pick, and some forms of Gaucher disease in \_\_\_\_\_.
Ashkenazi Jews
838
Mucopolysaccharidoses:
* autosomal recessive
* developmental delay
* gargoylism
* airway obstruction
* corneal clouding
* hepatosplenomegaly
Hurler syndrome
839
Mucopolysaccharidoses:
deficient in Hurler syndrome
α-L-iduronidase
840
Mucopolysaccharidoses:
accumulates in Hurler syndrome
* Heparan sulfate
* Dermatan sulfate
841
Mucopolysaccharidoses:
* X-linked recessive
* mild Hurler + aggressive behavior
* no corneal clouding
Hunter syndrome
**Hunters** see clearly (**no corneal clouding**) and aggressively aim for the **X** (**X**-linked recessive).
842
Mucopolysaccharidoses:
deficient in Hunter syndrome
Iduronate-2-sulfatase
843
Mucopolysaccharidoses:
accumulates in Hunter syndrome
* Heparan sulfate
* Dermatan sulfate
844
Fatty Acid Metabolism
845
Fatty acid synthesis requires transport of _____ from mitochondria to cytosol.
Citrate
“**SY**trate” = **SY**nthesis
846
Fatty acid metabolism predominantly occurs in \_\_\_\_\_.
* liver
* lactating mammary glands
* adipose tissue
847
Long-chain fatty acid (LCFA) degradation requires \_\_\_\_\_-dependent transport into the mitochondrial matrix.
Carnitine
**CAR**nitine = **CAR**nage of fatty acids
848
\_\_\_\_\_ is an inherited defect in transport of LCFAs into the mitochondria → toxic accumulation. Causes weakness, hypotonia, and hypoketotic hypoglycemia.
Systemic 1° Carnitine Deficiency
849
\_\_\_\_\_ causes ↓ ability to break down fatty acids into acetyl-CoA → accumulation of fatty acyl carnitines in the blood with hypoketotic hypoglycemia. Causes vomiting, lethargy, seizures, coma, liver dysfunction, hyperammonemia. Can lead to sudden death in infants or children. Treat by avoiding fasting.
Medium-Chain Acyl-CoA Dehydrogenase Deficiency
850
Ketone Body Metabolism
851
Ketone Bodies
* Acetone
* Acetoacetate
* β-hydroxybutyrate
852
In the liver, fatty acids and amino acids are metabolized to _____ to be used in muscle and brain.
* Acetoacetate
* β-hydroxybutyrate
853
In prolonged starvation and diabetic ketoacidosis, _____ is depleted for gluconeogenesis.
Oxaloacetate
854
In alcoholism, excess NADH shunts oxaloacetate to \_\_\_\_\_.
Malate
855
In prolonged starvation and diabetic ketoacidosis, oxaloacetate is depleted for gluconeogenesis. In alcoholism, excess NADH shunts oxaloacetate to malate. Both processes cause a buildup of \_\_\_\_\_, which shunts glucose, amino acids, and FFAs toward the production of ketone bodies.
Acetyl-CoA
856
Ketone bodies make the breath smell like \_\_\_\_\_.
Acetone (fruity odor)
857
Urine test for ketones can detect \_\_\_\_\_, but not β-hydroxybutyrate.
Acetoacetate
858
RBCs cannot utilize ketones; they strictly use \_\_\_\_\_.
glucose
859
HMG-CoA lyase is used for \_\_\_\_\_.
ketone production
860
HMG-CoA reductase is used for \_\_\_\_\_.
cholesterol synthesis
861
Metabolic Fuel Use
1g **carb**/protein (eg, **whey**) = **4** kcal
1g **alcohol** = **7** kcal
1g **fatty acid** = **9** kcal
\*# letters = # kcal
862
During fasting and starvation, priorities are to \_\_\_\_\_.
* supply sufficient glucose to the brain and RBCs
* preserve protein
863
Glycolysis and aerobic respiration occur during the \_\_\_\_\_.
Fed State (after a meal)
864
During the fed state (after a meal), _____ stimulates storage of lipids, proteins, and glycogen.
Insulin
865
Hepatic glycogenolysis (major), hepatic gluconeogenesis and adipose release of FFA (minor) occur during \_\_\_\_\_.
Fasting (between meals)
866
During fasting (between meals), _____ stimulate use of fuel reserves.
* Glucagon
* Epinephrine
867
During starvation (days 1–3), blood glucose levels aremaintained by:
* Hepatic glycogenolysis
* Adipose release of FFA
* Muscle and liver, which shift fuel use from glucose to FFA
* Hepatic gluconeogenesis from peripheral tissue lactate and alanine, and from adipose tissue glycerol and propionyl-CoA (from odd-chain FFA—the only triacylglycerol components that contribute to gluconeogenesis)
868
During starvation (after day 3), _____ are used and _____ become the main source of energy for the brain. After these are depleted, vital protein degradation accelerates, leading to organ failure and death. Amount of excess stores determines survival time.
adipose stores
ketone bodies
869
Glycogen reserves are depleted after _____ of starvation.
day 1
870
RBCs lack _____ and therefore cannot use ketones.
mitochondria
871
Energy Use in Starvation
872
Lipid Transport
873
\_\_\_\_\_ mediates transfer of cholesterol esters to other lipoprotein particles.
Cholesterol Ester Transfer Protein
874
Lipid Transport
875
Key Enzymes in Lipid Transport
* Hepatic Lipase
* Hormone-Sensitive Lipase
* Lecithin-Cholesterol Acyltransferase
* Lipoprotein Lipase
* Pancreatic Lipase
876
Key Enzymes in Lipid Transport:
degrades TGs remaining in IDL
Hepatic Lipase
877
Key Enzymes in Lipid Transport:
degrades TGs stored in adipocytes
Hormone-Sensitive Lipase
878
Key Enzymes in Lipid Transport:
catalyzes esterification of 2⁄3 of plasma cholesterol
Lecithin-Cholesterol Acyltransferase
879
Key Enzymes in Lipid Transport:
* degrades TGs circulating chylomicrons and VLDLs
* found on vascular endothelial surface
Lipoprotein Lipase
880
Key Enzymes in Lipid Transport:
degrades dietary TGs in small intestine
Pancreatic Lipase
881
Major Apolipoproteins
882
Apolipoproteins:
mediates remnant uptake
E
**E**verything **E**xcept LDL
883
Apolipoproteins:
activates LCAT
A-I
**A**ctivate
884
Apolipoproteins:
lipoprotein lipase cofactor that catalyzes cleavage
C-II
**C**ofactor that **C**atalyzes **C**leavage
885
Apolipoproteins:
* mediates chylomicron secretion into lymphatics
* only on particles originating from the intestines
B-48
886
Apolipoproteins:
* binds LDL receptor
* only on particles originating from the liver
B-100
887
Lipoproteins are composed of varying proportions of \_\_\_\_\_.
* cholesterol
* TGs
* phospholipids
888
\_\_\_\_\_ carry the most cholesterol.
LDL, HDL
889
\_\_\_\_\_ transports cholesterol from liver to tissues.
LDL
890
\_\_\_\_\_ transports cholesterol from periphery to liver.
HDL
891
\_\_\_\_\_ is needed to maintain cell membrane integrity and synthesize bile acid, steroids, and vitamin D.
Cholesterol
892
\_\_\_\_\_ deliver dietary TGs to peripheral tissues. The also deliver cholesterol to liver in the form of chylomicron remnants, which are mostly depleted of their TGs. They are secreted by intestinal epithelial cells.
Chylomicrons
893
\_\_\_\_\_ delivers hepatic TGs to peripheral tissue. It is secreted by liver.
VLDL
894
\_\_\_\_\_ is formed in the degradation of VLDL. It delivers TGs and cholesterol to liver.
IDL
895
\_\_\_\_\_ delivers hepatic cholesterol to peripheral tissues. It is formed by hepatic lipase modification of IDL in the liver and peripheral tissue. It is taken up by target cells via receptor-mediated endocytosis.
LDL
896
\_\_\_\_\_ mediates reverse cholesterol transport from periphery to liver. It acts as a repository for apolipoproteins C and E (which are needed for chylomicron and VLDL metabolism). It is secreted from both liver and intestine. Alcohol ↑ synthesis.
HDL
897
\_\_\_\_\_ is an autosomal recessive disease where chylomicrons, VLDL, and LDL are absent. There is a deficiency in ApoB-48, ApoB-100. Affected infants present with severe fat malabsorption, steatorrhea, and failure to thrive. Later manifestations include retinitis pigmentosa, spinocerebellar degeneration due to vitamin E deficiency, progressive ataxia, and acanthocytosis.
Abetalipoproteinemia
898
Abetalipoproteinemia is treated with \_\_\_\_\_.
* restriction of long-chain fatty acids
* large doses of oral vitamin E
899
Familial Dyslipidemias
* I—Hyperchylomicronemia
* II—Familial hypercholesterolemia
* III—Dysbetalipoproteinemia
* IV—Hypertriglyceridemia
900
Familial Dyslipidemias:
* autosomal recessive
* lipoprotein lipase or apolipoprotein C-II deficiency
I—Hyperchylomicronemia
901
Familial Dyslipidemias:
↑ chylomicrons, TG, and cholesterol
I—Hyperchylomicronemia
902
Familial Dyslipidemias:
* pancreatitis
* hepatosplenomegaly
* eruptive/pruritic xanthomas
* no ↑ risk for atherosclerosis
* creamy layer in supernatant
I—Hyperchylomicronemia
903
Familial Dyslipidemias:
* autosomal dominant
* absent or defective LDL receptors
* defective ApoB-100
II—Familial hypercholesterolemia
904
Familial Dyslipidemias:
↑ LDL, cholesterol, and VLDL
II—Familial hypercholesterolemia
IIa: LDL, cholesterol
IIb: LDL, cholesterol, VLDL
905
Familial Dyslipidemias:
* heterozygotes (1:500) have cholesterol ≈ 300mg/dL
* homozygotes (very rare) have cholesterol ≈ 700+ mg/dL.
* accelerated atherosclerosis (may
have MI before age 20)
* tendon (Achilles) xanthomas
* corneal arcus
II—Familial hypercholesterolemia
906
Familial Dyslipidemias:
* autosomal recessive
* defective ApoE
III—Dysbetalipoproteinemia
907
Familial Dyslipidemias:
↑ chylomicrons and VLDL
III—Dysbetalipoproteinemia
908
Familial Dyslipidemias:
* premature atherosclerosis
* tuberoeruptive xanthomas
* palmar xanthomas
III—Dysbetalipoproteinemia
909
Familial Dyslipidemias:
* autosomal dominant
* hepatic overproduction of VLDL
IV—Hypertriglyceridemia
910
Familial Dyslipidemias:
↑ VLD and TG
IV—Hypertriglyceridemia
911
Familial Dyslipidemias:
* hypertriglyceridemia (\> 1000 mg/dL) can cause acute pancreatitis
* related to insulin resistance
IV—Hypertriglyceridemia
