Step 1 Flashcards Excel 1 30 15
(500 cards)
1
Q
What makes up a nucleosome?
A
Negatively charged DNA loops twice around positively charged histone octamer.
2
Q
Histones have a lot of what?
A
Rich in lysine and arginine
3
Q
Purpose of H1
A
Binds to nucleosome and to linker DNA to stabilize the chromatin fiber: it is the only one NOT in the nucleosome core.
4
Q
DNA and histone synthesis during what phase of mitosis
A
S phase
5
Q
Nucleosome core histones
A
H2A, H2B, H3, H4 (each x2)
6
Q
Heterochromatin
A
Highly condensed, not active
7
Q
Euchromatin
A
Transcriptionally active
8
Q
DNA methylation in prokaryotes
A
Template strand Cs and As are methylated to allow mismatch repair enzymes to distinguish parent from daughter strand.
9
Q
DNA methylation in eukaryotes
A
CpG islands to repress transcription
10
Q
What are CpG islands exactly?
A
Cytosine next to Guanine in a strand of DNA. The cytosine can be methylated, in fact most of the cytosines in CpG islands are.
11
Q
Histone methylation
A
Usually reversible, represses transcription, but can occasionally activate it.
12
Q
Histone acetylation
A
Relaxes DNA coiling, increasing transcription
13
Q
What are the pyrmidines
A
Pyrimidines CUT
14
Q
Thymine vs Uracil
A
Thymine has a methyl, uracil is a deaminated cytosine
15
Q
Amino acids necessary for purine synthesis
A
GAG-Glycine, Aspartate, Glutamine
16
Q
What makes up pyrimidines?
A
Carbamoyl phosphate and aspartate
17
Q
Nucleoside vs. nucleotide
A
nucleoside is base + sugar, -tide has 3’-5’ phosphodiester bond linked phosphate(s)
18
Q
Basic steps of Purine synthesis
A
- Star with sugar + phosphate (PRPP) 2. Add base
19
Q
What is PRPP?
A
Phosphoribosyl pyrophosphate (it has a phosphate instead of a base attached to the ribose)
20
Q
Basic steps of Pyrimidine synthesis
A
- Make temporary base (orotic acid) 2. Add sugar + phosphate (PRPP) 3. Modify base
21
Q
What turns ribonucleotides to deoxyribonucleotides
A
Ribonucleotide reductase
22
Q
Carbamoyl phosphate used in what metabolic pathways
A
De novo pyrimidine synthesis and the urea cycle
23
Q
Purine base production steps
A
- Start with Ribose 5-P2. Turn to PRPP by PRPP synthetase3. Produce IMP through some steps4. AMP and GMP produced (GMP by IMP dehydrogenase?)
24
Q
What does de novo purine synthesis require?
A
Aspartate, glycine, glutamine, and THF
25
Pyrimidine base production steps
1. Combine Glutamine and CO2 with Carbamoyl phosphate synthetase II to produce carbamoyl phosphate (uses up two ATP)2. Carbamoyl phosphate + Asparate to produce Orotic Acid3. Orotic acid + PRPP to produce UMP4. UMP to UDP5. UDP to CTP or dUDP with ribonucleotide reductase6. dUDP to dUMP7. dUMP to dTMP by Thymidylate synthase8. Tetrahydrofolate in N5N10methyleneTHF is what is used to add the methyl group.
26
Draw out the pathways!
Writing them out isn't very useful.
27
Leflunomide target
Inhibits dihydroorotate dehydrogenase
28
Mycophenolate and ribavirin target
Inhibit IMP dehydrogenase
29
Hydroxyurea target
Ribonucleotide reductase
30
6-mercaptopurine (6-MP) target AND its prodrug
Prodrug is azathioprine. They both inhibit de novo purine synthesis.
31
5-fluorouracil (5-FU) target
Inhibits thymidylate synthase (lowers deoxythymidine monophosphate (dTMP))
32
Methyotrexate (MTX), Trimethoprim (TMP), and pyrimethamine target
Inhibits Dihydrofolate reductase (lowers dTMP) in humans, bacteria, and protozoa, respectively. (MTX in humans, TMP in bacteria, Pyrimethamine in protozoa)
33
Does myophenolate/ribavirin only affect GMP production?
Yes, for de novo GTP production.
34
Guanine to Cuanylic acid (GMP)
HGPRT + PRPP
35
Hypoxanthine to Inosinic acid (IMP)
HGPRT + PRPP
36
Adenine to Adnylic acid (AMP)
APRT + PRPP
37
Adenosine to Inosine
Adenosine deaminase (ADA)
38
Hydroxanthine to Xanthine
Xanthine oxidase
39
Xanthine to uric acid
Xanthine oxidase
40
Draw out the purine salvage deficiencies
...
41
Adenosine deaminase deficiency path
Excess ATP and dATP imbalances nucleotide pool via feedback inhibition of ribonucleotide reductase leading to the prevention of DNA synthesis and thus lower lymphocyte count
42
Adenosine deaminase deficiency and what disease
Autosomal recessive SCID (one of the major causes)
43
Lesch-Nyhan path
Defective purine salvage from absence of HGPRT. Excess uric acid production and de novo purine synthesis.
44
Lesch-Nyhan genetics
X-linked recessive
45
Lesch-Nyhan presentation
Intellectual disability, self-mutilation, aggression, hyperuricemia, gout, dystonia.
46
Lesch-Nyhan tx
Allopurinol or febuxostate (2nd line)
47
Lesch-Nyhan Mnemonic
HGPRT: Hyperuricemia, Gout, Pissed off (aggressin,self-mutilation), Retardation, Dystonia
48
What is HGPRT?
Hypoxantine-Guanine Phosphoribosyltransferase
49
Degenerate code
Multiple codons for most amino acids
50
Methionine codon
AUG
51
Tryptophan codon
UGG
52
What is commaless, nonoverlapping code?
Commaless means that no codons are used as punctuation, it is read straight through (at least the exons, etc.). Nonoverlapping means one codon in a sequence leads to one amino acid. In viruses, the genes can overlap.
53
Universal code exception
Mitochondria in humans. The codons can be a little different.
54
Origins of replication in prok. and euk.
Prok. have 1! (theta-replication)Euk. have multiple (large chromosomes)
55
Single-stranded binding proteins
Prevent strands from reannealing
56
DNA topoisomerases
Create single or double-stranded breaks in helix to add or remove supercoils
57
Fluoroquinolones action
Inhibit DNA gyrase (prok. topoisomerase II)
58
Primase
RNA primer for DNA pol III initiation
59
DNA pol III
Prok. only, 5'-3' replication, 3'-5' exonuclease activity (proofreading). On lagging strand, reads until it gets to primer
60
DNA pol I
Prok. only. Replaces RNA primer with DNA. 5'-3' exonuclease activity
61
DNA ligase
Joins Okazaki fragments
62
Telomerase
RNA-dependent DNA polymerase that adds DNA to 3' ends of chromosomes to avoid loss of genetic material with every duplication.
63
HGPRT role
Recycling back to nucleic acids. Guanine to GMP, Hypoxanthine to IMP (moves away from xanthine and uric acid!!)
64
APRT role
It is the HGPRT for Adenine. Adenine to AMP.
65
What is the order of severity of mutations to the genetic code
silent<
66
Most silent mutations found where in codon
In the 3rd position (wobble!)
67
Sickle cell caused by what mutation
Missense
68
How to get a frameshift
Delete or add nucleotides not a multiple of 3.
69
What mutation is duchenne's
Frameshift
70
I have a bulky helix-distorting DNA lesion, what do I use?
Nucleotide excision repair. Removes an oligonucleotide containing the damage then DNA pol and ligase fills it in. Pyrimidine dimers and bulky chemical adducts.
71
I have an altered Base
Base excision repair
72
Base excision repair:
Base-specific glycosylase recognizes altered base and creates AP site (apurinic,apyrimidinic). One or more nucleotides are removed by AP-endonuclease, which cleaves the 5' end. Lyase cleaves the 3' end. DNA pol-beta fills the gap and DNA ligase seals it.
73
AP-endonuclease action
Forms a single strand break. DNA glycosylase just removes the base by cleaving the N-glycosidic bond. AP endonuclease cleaves the 5' end of the AP site
74
Lyase action
Cleaves 3' end of AP site
75
Mismatch repair vs. Nucleotide exicision repair
Nucleotide excision for bulky adducts or major distortions to the DNA helix.
76
Mismatch repair
Repairs errors that occur during DNA synthesis. Usually just transitional errors (laying a C instead of T)
77
Xeroderma pigmentosum problem
Nucleotide excision repair, prevents repair of pyrimidine dimers because of UV exposure
78
Spontaneous/toxic deamination repair
Base excision repair. It's the reason why DNA has thymine, because when it deaminates it turns methylated cytosine which is recognizable. Not cytosine if we had uracil instead.
79
Hereditary nonpolyposis colorectal cancer problem
Mismatch repair
80
Ataxia telangiectasia problem
Nonhomologous end joining
81
Nonhomologous end joining problem
Repairs double stranded breaks. No requirement for homology.
82
Energy for DNA/RNA production
5' end of incoming nucleotide bears the triphosphate
83
Protein synthesis direction
N-terminus to C-terminus
84
mRNA read
5' to 3'
85
Phosphate bond reaction
Triphosphate bond targeted by the 3' hydroxyl attack.
86
How to block DNA replication
Modified 3' OH, preventing addition of the next nucleotide (chain termination)
87
mRNA start codons
AUG (rarely GUG):
88
AUG codes for
Euk. methionine which may be removed before translation ends. Prok. formylmethionine (f-met.)
89
mRNA stop codons
UAA, UGA, UAG (u are annoying, u go away, u are gone)
90
Promoter regions
TATA boxes and CAAT boxes (weak bonds, easy to open)
91
Enhancers bind
Transcription factors, may be found in introns
92
Silencers bind
Repressors, may be found far away, close to, or in an intron, like enhancers.
93
Most numerous RNA
rRNA (in ribosomes)
94
Largest RNA
mRNA
95
Smallest RNA
tRNA
96
RNA pol I
rRNA
97
RNA pol II
mRNA
98
RNA pol III
tRNA
99
Euk. or prok. have 3 RNA pol
Euk. have 3 RNA pol, prok. have just 1.
100
alpha-amanitin path
inhibits RNA pol II, severe hepatotoxicity, found in Amanita phalloides (death cap mushrooms)
101
Initial mRNA from transcription is called
Heterogenous nuclear RNA (hnRNA)
102
mRNA processing
1. 5' cap (7-methylguanosine cap)2. Polyadenylation at 3' end (around 200 A's)3. Splicing out introns
103
mRNA quality control
Cytoplasmic P-bodies, contain exonucleases, decapping enzymes, and microRNAs; mRNAs may be stored here for future translation
104
What are P-bodies?
Processing bodies. Decaps and degrades unwanted mRNAs. Stores mRNA for later translation. Aids in translation repression with miRNAs (like siRNAs)
105
Poly-A polymerase template
No template needed
106
Polyadenylation signal
AAUAAA
107
Splicing
1. Primary transcript combines with small nuclear ribonucleoproteins (snRNPs) and other proteins to form spliceosome. 2. Lariat-shaped intermediate is generated 3. Lariat is released to precisely remove intron
108
Splicing mechanistically
A 3' OH is formed during lariat formation which then allows for an attack at the phosphodiester bond at the 2nd exon leading to splicing out the intron.
109
anti-smith antibodies
Antibodies to spliceosomal snRNPs (anti-Smith antibodies). Highly specific for SLE.
110
Anti-U1 RNP antibodies
Highly associated with MCTD
111
Draw out splicing reaction
....
112
Abnormal splicing can cause what
Oncogenesis, Beta-thal
113
Exons vs. introns
Exons are coding
114
tRNA structure
75-90 nucleotides. Cloverleaf. CCA at 3' end which binds the amino acid. Anticodon end is opposite 3' aminoacyl end. The A in CCA binds the aminoacid.
115
T-arm of tRNA
Contains TPsyC (thymine, pseudouridine, cytosine) sequence necessary for tRNA-ribosome binding.
116
D-arm of tRNA
Contains dihydrouracil residues necessary for tRNA recognition by the correct aminoacyl-tRNA synthetase.
117
Acceptor stem of tRNA
The 3' CCA is the amino acid acceptor site
118
tRNA charging
Aminoacyl-tRNA synthetase checks AA before and after binding to tRNA, if incorrect, it hydrolyzes it because you can't fix it afterwards.
119
How many amino acids for each aminoacyl-tRNA synthetase
One synthetase for every AA
120
Aminoacyl-tRNA synthesis reaction energy
ATP used to make the bond, but the new bond is used to form the peptide bond.
121
Anticodon for start codon
UAC (binding to AUG)
122
tRNA wobble
Only first 2 nucleotide positions of an mRNA codon matter
123
Initiation of translation
GTP hydrolysis; initiation factors assemble 40S with initiator tRNA and are released when the mRNA and 60S assemble with the complex
124
Euk. ribosome
40S + 60S = 80S (Even (euk.))
125
Prok. ribosome
30S + 50S = 70S (Odd (prOk.))
126
ATP-tRNA
Activation (charging)
127
GTP-tRNA
Gripping and Going places (translocation)
128
Initiator methionine binds where
P site
129
Steps in translation
Aminoacyl-tRNA binds to A site, peptide bond forms, translocation 3 nucleotides over and repeat.
130
Stop codon reached, then what
Release factor comes in and releases the polypetide
131
A, P, and E sites
Aminoacyl, peptide, and exit.
132
Posttranslational modifications
Cleaving N- or C-terminus of zymogen. Phosphorylation, glycosylation, hydroxylation, methylation, acetylation, and ubiquitination.
133
What are heat shock proteins
e.g. Hsp60, in yeast, are chaperonins expressed at high temps to prevent protein denaturing/misfolding.
134
Chaperone proteins
Can facilitating or maintain protein folding.
135
What regulates cell cycle phases
Cyclins, cyclin-dependent kinseases (CDKs), and tumor suppressors.
136
Which phases are variable in time
G1 and G0. Not G2, when that begins, there is a set time for when it must go to mitosis.
137
Order of the phases
G1/G0 to S phase to G2 to Mitosis.
138
What regulates G1 to S phase progression.
Rb, p53
139
CDKs action
Constitutive and inactive...????
140
Cyclins
Regulatory proteins that control cell cycle events; phase specfic; activate CDKs
141
Cyclic-CDK complexes
Must be both activated and inactivated for cell cycle to progress
142
p53 and Rb
Hypophophorylated Rb and p53 normally inhibit G1-to-S progression
143
What happens if you mutate p53 or Rb
Unrestrained cell division (e.g. Li-Fraumeni)
144
What is interphase
G1, S, and G2
145
What cell lines are G0
Neurons, skeletal and cardiac muscle, RBCs. These are permanent
146
What cells go from G0 to G1
Hepatocytes, lymphocytes. These are quiescent.
147
What cells never go to G0
Bone marrow, gut epithelium, skin, hair follices, germ cells
148
Rough ER purpose
Site of synthesis of secretory (exported) proteins and of N-linked oligosaccharide addition to many proteins
149
Example of cells with lots of RER
Mucus-secreting goblet cells of the small intestine and antibody-secreting plasma cells
150
Nissl bodies
RER in neurons, synthesize peptide neurotransmitters for secretion
151
What do free ribosomes do
Site of synthesis of cytosolic and organella proteins
152
Smooth ER purpose
Steroid synthesis and detox of drugs and poisons.
153
Cells with lots of SER
Liver hepatocytes and steroid hormone-producing cells of the adrenal cortex and gonads
154
Golgi purpose
Movies proteins and lipids from the ER to vesicles and plasma membrane.
155
Example of specific effects of Golgi
Modifies N-oligosaccharides on asparagine. Adds O-oligosacchardies on serine and threonine. Adds mannose-6-phophate to proteins for trafficking to lysosomes.
156
Mannose-6-phosphate
...
157
Endosomes purpose
Take stuff from outside the cell or from the Golgi, sending it to lysosomes for destruction or back to the membrane/Golgi for further use.
158
Inclusion cell disease (I-cell disease) path
Inherited lysosomal storage disorder; defect in phosphotransferase. Golgi can't phosphorylate mannose residues (i.e. dec. mannose-6-phosphate) on glycoproteins leading to extracellular excretion and not delivered to lysosomes.
159
I-cell disease presentation
Coarse facial features, clouded corneas, restricted joint movement, and high plasma levels of lysosomal enzymes. Often fatal in childhood.
160
Signal recognition particle (SRP)
Abundant, cytosolic ribonucleoprotein that traffics proteins from the ribosome to the RER. Absent or dysfunctional SRP leads to proteins accumulating in the cytosol.
161
Vesicular trafficking proteins
COPI, COPII, and Clathrin.
162
COPI functions
Golgi to Golgi (retrograde); Golgi to ER
163
COPII functions
Golgi to Golgi (anterograde); ER to Golgi
164
Clathrin functions
trans-Golgi to lysosomes; plasma membrane to endosomes (receptor mediated endocytosis (LDL receptor))
165
Peroxisome
Catabolism of very-long-chain fatty acids, branched-chain fatty acids, and amino acids
166
Proteasome
Breaks down damaged or ubiquitin tagged proteins. Defects in teh ubiquitin-proteasome system have been implicated in some cases of Parkinson's.
167
Microtubule structure
Helical cylinder of polymerized heterodimers of alpha and beta-tubulin. Each dimer uses 2 GTP.
168
Microtubule location
Flagella, cilia, mitotic spindles
169
Microtubule growth
Grow slowly (at positive end), collapse quickly
170
Microtubule in neurons
Slow axoplasmic transport
171
Molecular motor proteins
Dynein (retrograde to microtubule (+ to -)Kinesin (anterograde to microtubule (- to +)
172
Drugs acting on Microtubules
Microtubules Get Poorly Very Poorly: Mebendazole, Griseofulvin, Colchicine, Vincristine/Vinblastine, Paclitaxel
173
Cilia structure
9+2 microtubule pair arragement with dynein ATPase linking peripheral 9 doublets
174
Kartageners syndrome presentation
Primary ciliary dyskinesia. Male and female infertility from immotile sperm and dysfunctional fallopian tube cilia. Increased risk of ectopic. Can cause bronchiectasis, recurrent sinusitus, and situs inversus.
175
Actin and Myosin found in
Muscles, microvilli, cytokinesis, adherens junctions.
176
Myosin structure
Dimeric, ATP driven motors
177
Intermediate filaments examples
Used for structure, vimentin, desmin, cytokeratin, lamins, glial fibrillary acid proteins (GFAP), neurofilaments.
178
Fungal membranes contain what
Ergosterol
179
What tissue stains vimentin
Connection
180
Tissue stain desmin
Muscle (desMin)
181
Tissue stain Cytokeratin
Epithelial Cells
182
GFAP tissue
NeuroGlia
183
Neurofilaments tissue
Neurons
184
Na/K ATPase
3 Na out, 2 K in. Net charge of 1 + out.
185
Toxins on Na/K ATPase
OuabainCardiac glycosides (digoxin and digitoxin)
186
Cardiac glycosides action
Directly inhibit the Na/K ATPase, which leads to indirect inhibition of Na/Ca exchange leading to increased intracellular calcium and increased cardiac contractility. Too much sodium in cell prevents movement of calcium into outside.
187
Oubain MOA
Inhibits K+ binding
188
ATP at what site of Na/K ATPase
Intracellular, fires when the sodium is released (first step). K+ comes in last
189
Which cartilage is the most common
Type I: 90%
190
Where do you find Type I, II, III, and IV cartilages (The Important Sites)
I: BoneII: Cartilage (cartwolage)III: Blood vessels (big one)IV: Under the floor (four/basement membrane)
191
Type I cartialge
Bone (osteoblasts), skin, tendon, dentin, fascia, cornea, late wound repair.
192
Type II cartilage
Cartilage (including hyaline), vitreous body, nucleus pulposus.
193
Type III cartilage
Reticulin: Skin, blood vessels, uterus, fetal tissue, granulation tissue
194
Type IV cartilage
Basement membrane, basal lamina, lens
195
Alport syndrome path
Defective Type IV collagen
196
Goodpasture path
Autoantibodies to Type IV
197
Vascular type of Ehlers-Danlos syndrome)
Type III; uncommon type!
198
Mnemonic for cartilage
Be So Totally Cool, Read Books. BST C R B
199
Osteogenesis imperfecta type I
Type I cartilage decreased production
200
Collagen synthesis steps
1. Synthesis 2. Hydroxylation 3. Glycosylation 4. Exocyotosis 5. Proteolytic processing 6. Cross-linking
201
1. Collagen Synthesis step
Translation of collagen alpha chains (preprocollagen): Gly-X-Y (X and Y are proline or lysine)
202
Amino acids that make up collagen
Glycine, proline, and lysine
203
2. Collagen hydroxylation step
Hydroxylation of specific proline and lysine residues requiring vit C
204
3. Collagen glycosylation step
Glycosylation of pro-alpha-chain hydroxyline residues and formation of procollagen via hydrogen and disulfide bonds (triple helix of 3 collagen alpha chains). Then leads to 4. Exocytosis
205
Osteogenesis imperfecta path
Can't form triple helix of procollagen.
206
What steps happen in the RER
Synthesis, hydroxylation, and glycosylation.
207
Look at a figure for Collagen synthesis steps
....
208
5. Proteolytic processing of collagen
Cleavage of disulfide-rich terminal regions of procollagen, transforming it into insoluble tropocollagen.
209
6. Cross linking of collagen
Staggered tropocollagen molecules reinforced by covalent lysine-hydroxylysine cross-linkage (by Cu2+-containing lysyl oxidsae) to make collagen fibrils.
210
Ehlers-Danlos path
You can't cross link collagen properly.
211
Osteogenesis imperfecta presentation
Brittle bone disease. Multiple fractures from minimal trauma. Blue sclerae because of translucency over the choidal veins. hearing loss (abnormal ossicles). Dental imperfections due to lack of dentin. May be confused with child abuse.
212
Osteo. Imp. genetics
Most common form is Aut. dom. with decreased production of otherwise normal type I collagen.
213
Ehlers-Danlos presentation
Hyperextensible skin, tendency to bleed (easy bruising), and hypermobile joints. May be associated with joint dislocation, berry and aortic aneurysms, and organ rupture.
214
Ehlers-Danlos types
6+ types. May be aut. dom. or rec. Hypermobility type: Most COMMON. Classical type (joint and skin symptoms): Mutation in type V collagen. Vascular type (vascular and organ rupture): Deficient type III collagen
215
Menkes disease
Connective tissue disease caused by impaired copper absorption and transport. Leads to decreased activity of lysyl oxidase (copper is a necessary cofactor). Results in brittle, kinky hair, growth retardation and hypotonia.
216
Elastin is found where
Skin, lungs, large arteries, elastic ligaments, vocal cords, ligamenta flava
217
Elastin structure
Rich in proline and glycine, nonhydroxylated forms. ????
218
Tropoelastin with fibrillin scaffolding?
....??
219
Elastin cross-linking
Takes place extracelluarly and gives elastin its elastic properties
220
What breaks down and prevents breakdown of elastin?
Elastase breaks down, inhibited by alpha1-antitrypsin.
221
Marfan syndrome
Defect in fibrillin, a glycoprotein that forms a sheath around elastin
222
Emphysema
Can be caused by alpha1-antitrypsin deficiency
223
Wrinkles of aging caused by
Lower collagen and elastin production
224
Diagnosing neonatal HIV or herpes encephalitis
PCR
225
Southern blot steps
DNA electrophoresed on gel then transferred to filter. Then denatured and exposed to radiolabeled DNA probe.
226
Northen blot
RNA
227
Western blot
Protein with antibody probe
228
Confirmatory test for HIV
Western blot after + ELISA
229
Southwestern Blot
DNA-binding proteins (Transcription factors) using labeled oligonucleotide probes
230
Microarrays benefits
Can profile gene expression levels of thousands of genes simultaneously to study diseases and treatments. Can detect SNPs and copy number variations (CNVs) for genotyping, clinical genetic testing, forensic analysis, cancer mutations, and genetic linkage analysis.
231
Collagenases are what kind of enzyme
MMP matrix metalloproteinases
232
Marfan's gene
Fibrillin-1 gene
233
The PI3K/Akt/mTOR pathway
anti-apoptosis, cellular proliferation, and angiogenesis. mutations in these lead to cancer pathogenesis
234
IP3
activates Protein Kinase C
235
Branched chain fatty acids undergo what for breakdown
Alpha-oxidation
236
problems with ubiquitin-proteasome system can lead to
Parkinson and Alzheimer's
237
Mousy odor in a child with fair colored features
Phenylketonuria. Tyrosine is an essential enzyme because they can't make it from phenylalanine anymore. Can't produce melanin either.
238
PKU caused by
mutation in phenylalanine hydroxylase enzyme
239
Nitrates in diet do what to DNA
deaminate cytosines, adenines, and guanines
240
In base excision repair....
AP endonuclease cleaves 5' side before lyase cleaves 3' side
241
Iron deficient anemia can present with
Dysphagia (esophageal webs) and dysfigured fingernails (spoon nails (koilonychia))
242
Plummer-Vinson or Patterson Kelly syndrome
Iron deficiency anemia with dysphagia from esophageal webs??
243
Pernicious anemia classic presentation
Older, mentally slow woman of northern European descent who is "lemon colored" (anemic and icteric) with a smooth shiny tongue of atrophic glossitis and a broad shuffling gait.
244
Cobalamin deficiency path
Homocystinemia due to impaired methionine re-synthesis.
245
Maturing erythrocytes lose the ability to synthesize heme when what happens...
When they lose their mitochondria
246
HbC is made of what
Lysine instead of glutamate residue so the Hb molecule is more positive and does not electrophorese as far compared to even HbS (valine is nonpolar)
247
ELISA stands for
Enzyme-linked immunosorbent assay
248
Indirect ELISA
A test antigen used to determine if an antibody is in the patient's blood, second antibody used to detect the first antibody.
249
Direct ELISA
Test antibody used to detect antigen in patient's blood, second antibody is used to detect the antigen
250
Positive ELISA result
Lights up brightly
251
Indirect ELISA test
anti-HIV antibody detection
252
Fluorescent in situ hybridization.
Using fluorescent DNA or RNA probe to bind specific gene site of interest on chromosomes.
253
Uses of FISH
Microdeletions that can't be detected by karyotype
254
Steps of cloning
Isolate euk. mRNA, use reverse transcriptase to make cDNA, insert cDNA into bacterial plasmids with ABx resistance genes, transform recombinant plasmid into bacteria, grow on Abx medium to get the bacteria that produces the cDNA.
255
How to get DNA into a mouse
1. Random insertion into mouse genome. 2. Trageted insertion or deletion of gene through homologous recombination with mouse gene.
256
What is homologous recombination
Uses a complementary dsDNA template (like the other chromosome) to fix dsDNA breaks. Can also be used for cloning.........
257
Cre-lox system
Can induce genes at specific developmental points...................................
258
RNA interference (RNAi)
dsRNA complementary to target mRNA used to degrade target mRNA
259
What tissues can be karyotypes
blood, bone marrow, amniotic fluid, or placental tissue.
260
alpha1-antitrypsin deficiency is inherited in what way
Codominance.............
261
Neurofibromatosis type 1 inheritance
variable expressivity
262
Example of pleiotropy
PKU with light skin, retardation, and musty body odor
263
what diseases have anticipation
Huntington, fragile x, myotonic dystrophy
264
Do oncogenes need loss of heterogeneity
No, loss of heterogeneity only applies to tumor suppression genes
265
Explain dominant negative mutation
It's a dominant mutation but it has the the negative, suppressive effect. Like a nonfunctional transcription factor preventing the functional wildtype protein from working.
266
Linkage disequilibrium for individuals or population
Measured in a population, not in a family
267
When is McCune-Albright a viable condition
Only if it is inherited mosaically
268
What is McCune-Albright syndrome
Genetic syndrome with 2 out of 3 of following: autonomous endocrine excess (e.g. precocious puberty), polyostotic fibrous dysplasia, unilateral cafe au lait spots.
269
What is locus heterogeneity
Mutations at different loci producing the same phenotype
270
What is allelic heterogeneity
Different mutations in the same locus produce the same phenotype
271
Heteroplasmy
Having normal and mutated mtDNA, causes variable expression in mitochondrial inherited disease.
272
How is homologous recombination used in cloning
.....
273
Uniparental disomy
Receiving 2 copies of a chromosome from one parent. and 0 from the other.
274
Hetero vs. isodisomy
Hetero occurs in meiosis I, iso in meiosis II. Iso can also happen post-zygotically with a chromosomal duplication and loss of the other chormosome.
275
When to consider UPD
When an individual has a recessive disorder but only one parent is carrying the trait.
276
How bad is UPD usually
Usually normal phenotype
277
Frequency of an X-linked recessive disease in males and females
males: qfemales: q^2
278
Hardy-Weinberg equillibrium requires
No mutation occurring at the locus, natural selection is not occuring, completely random mating, no net migration
279
Prader-Willi and Angelman on what chromosome
15
280
Prader-Willi inheritance
Prader lacks Faddah. Maternal imprinting: maternal gene is silent and paternal gene is deleted/mutated
281
AngelMan inheritance
Misses Muddah. Dad gene is normally silent and maternal gene is deleted/mutated.
282
P-W presentation
Hyperphagia, obesity, intellectual disability, hypogonadism, and hypotonia
283
Angelman presentation
Inappropriate laughter (happy puppets, seizures, ataxia, and severe intellectual disability)
284
Specific genetics about P-W
25% of cases due to maternal UPD, remaining are mutuation or deletion
285
Specific genetics about Angelman
5% of cases due to paternal UPD, remaining are mutuation or deletion
286
Are P-W and Angelman genes on maternal and paternal side both normally silent????
No...one is usually active. So if you lack the father's chromosome from deletion but the maternal side is not imprinted...will you not have the disease. Or is one or the other imprinted........................
287
Which diseases tend to be worse, aut. rec or aut. dom.
Aut. rec., they tend to pop up in childhood, aut. dom. are often pleiotropic
288
Why aren't x-linked recessive passed male to male
Because the father gives the son the Y chromosome
289
X-linked dom. inheritance
Mothers pass on to 50% of sons AND daughters, fathers transmit to all daughters but no sons
290
Example of x-linked dom. inheritance
Hypophosphatemic rickets
291
Hypophosphatemic rickets
vitamin-D resistant rickets. Increased phosphate wasting and proximal tubule.
292
Mitochondrial myopathies presentation
Myopathy, lactic acidosis, and CNS disease, secondary to failrue in ox phos
293
Muscle biopsy of mitochondrial myopathies
Ragged red fibers
294
Autosomal dominant polycystic kidney disease genetics
85% of cases due to mutation in PKD1 (chromosome 16); remainder due to mutation in PDK2 (chrom. 4)
295
Familial adenomatous polyposis genetics
APC gene, chrom. 5
296
Familial hypercholesterolemia
Defective/absent LDL receptor, can have tendon xanthomas (Achilles!!)
297
Hereditary hemorrhagic telangiectasis
Telangiectasia, recurrent epistaxis, skin discolorations, AVMs, GI bleeding, hematuria.
298
Hereditary spherocytosis genetics
spectrin or ankyrin defects
299
Hereditary spherocytosis CBC w/ diff results
Elevated MCHC
300
Huntington genetics
Chrom 4, trinucleotide repeat disorder (CAG)n.
301
Marfan's genetics
fibrillin-1 gene mutation
302
Marfan syndrome presentation
Tall with long extremities, pectus excavatum, hypermobile joints, and long, tapering fingers and toes (arachnodactyly), cystic medial necrosis of aorta leading to aortic incompetance and dissecting aortic aneurysms, floppy mitral valave. Subluxation of lenses upward and temporally.
303
MEN2 gene
ret gene
304
NF1 (von Recklinghausen disease)
Neurocutaneous: cafe-au-lait spots, cutaneous neurofibromas, aut. dom., 100% penetrance, variable expression. CHROMOSOME 17
305
NF2
Bilateral acoustic schwannomas, juvenile cataracts, meningiomas, and ependymomas. CHROMOSOME 22
306
Tuberous sclerosis
neurocutaneous disorder with numerous benign hamartomas, incomplete penetrance, variable expression
307
von Hippel-Lindau disease
VHL gene (tumor suppressor) on chromosome 3 (3p).
308
Cystic fibrosis genetics
Aut. rec, CFTR gene on chrom. 7, most commonly a deletion of Phe508, most common lethal genetic disease in caucasians
309
Function of CFTR gene
ATP-gated Cl- channel that secretes cl- in lungs and GI tract and reabsorbs Cl- in sweat glands.
310
CF patho
mutations cause misfolded protein that is retained in RER and not transported to cell membrane leading to less Cl- (and H2O) secretion and more Na+ reabsorption to compensate for incrased ICF cl- leading to even less ECF water causing very thick mucus
311
CF membrane potential
Increased Na+ reabsorption causes mroe negative transepithelial potential difference....how....I thought the inside is negative because the na/k atpase pushes an extra cation out, wouldn't this just ruin the membrane potential.
312
CF diagnosis
Cl- conc. >60 mEq/L in sweat is diagnostic, can cause a contraction and hypokalemia (ECF effects like taking a loop diuretic) Renal K+/H+ wasting
313
CF CXR
Reticulonodular pattern
314
CF genitals
Infertile men (no vas deferens, no sperm)
315
CF PNA
recurrent Pseudomonas
316
CF tx
N-acetylcysteine to loosen mucus plugs (cleaves disulfide bonds within mucus glycoproteins). Dornase alfa (DNAse) to clear leukocytic debris
317
X-linked recessive disorders
Be Wise, Fool's GOLD Heeds Silly HOpe.Bruton agammaglobulinemia, Wiskott-Aldrich syndrome, Fabry disease, G6PD deficiency, Ocular albinism, Lesch-Nyhan syndrome, Duchenne (and Becker) muscular dystrophy, Hunter Syndrome, Hemophilia A and B, Ornithine transcarbamoylase deficiency
318
CF transepithelial potential difference
More negative because more sodium is being reabsorbed. This is different from membrane potential because I think that actually goes up because of the sodium rushing in, unless the Cl- still makes it more negative.
319
Duchenne mutation
X-linked frameshift
320
Gower manuever
using upper extremities to help kids stand up
321
Duchenne age of onset
Before 5 yrs
322
MCC of death in Duchenne's
dilated cardiomyopathy
323
Dystrophin purpose
connects intracellular cytoskeleton (actin) to the transmembrane proteins alpha and beta-dystroglycan, which are connected to the ECM. without in you get myonecrosis
324
Duchenne's bloodwork
Increased CPK and aldolase scene
325
Duchenne's dx
Western blot and muscle biopsy confirm diagnosis
326
Becker mutation
X-linked point mutation
327
Becker onset
Adolescene or early adulthood
328
Myotonic dystrophy type 1 genetics
CTG trinucleotide repeat expansion in the DMPK gene leading to abnormal expression of myotonin protein kinase
329
Myotonic type 1 presentation
Myotonia, muscle wasting, frontal balding, cataracts, testicular atrophy, and arrhythmia
330
Myotonia is
Delayed relaxation with prolonged contraction, muscle may be warmed up to limit the myotonia
331
Fragile X genetics
FMR1 gene on X chrom. affecting the methylation and expression of the FMR1 gene.
332
Fragile X epidemiology
2nd MCC of genetic intellectual disability (after Down's)
333
Fragile X presentation
Post-pubertal macroorchidism (enlarged testes), long face with a large jaw, large everted ears, autism, mitral valve prolapse
334
Fragile X genetic path
Trinucleotide repeat disorder (CGG)
335
Fragile X mnemonic
eXtra large testes, jaw, and ears
336
GAA
Friedreich ataxia
337
CAG
Huntington
338
CTG
Myotonic dystrophy
339
CGG
Fragile X
340
Mnemonic for Trinucleotide repeat disorders
X-Girlfriend's First Aid Helped Ace My Test (the middle letter of each repeat)
341
Down syndrome presentation
MR, flat facies, epicanthal folds, palmar crease, gap between 1st 2 toes, duodenal atresia, Hirschsprung's, congenital heart disease (ostium primum-type ASD), Brushfield spots. Inc. risk of ALL, AML< and Alzheimer's (>35 years old)
342
Down's genetics
1:700. 95% due to nondisjunction. 4% due to reobersonian translocation. 1% due to mosaiciism (post-fertilization mitotic error)
343
Down syndrome First trimester diagnosis
US: Inc. nuchal translucency and hypoplastic nasal boneSerum: PAPP-A is down, betahCG is up
344
Down syndrome Second trimester diagnosis
Serum: low AFP, high beta-hCG, low estriol, inc. inhibin A
345
Edwards syndrome presentation
Severe MR, rocker-bottom feet, micrognathia, low set Ears, clenched hands, prominent occiput, cong. heart disease, death within 1 yr
346
Edwards syndrome genetics
(E)lection age (18)1:8000, most common trisomy resulting in live birth after Down's
347
Edwards serum
PAPP-A and free betahCG down in first trimester. Quad screen: low AFP, low betahCG, low estriol, low or normal inhibin A
348
Patau syndrome presentation
severe MR, rocker bottom feet, microphthalmia, microcephaly, cleft liP/Palate, holoProsencephaly, Polydactyly, congenital heart disease, death within 1 yr
349
Patau genetics
(P)uberty 13
350
Patau serum
First-trimester: low betahCG, low PAPP-A and increased nuchal translucency
351
Draw out a table of the three viable trisomies bloodwork in pregnancy
....
352
Draw out nondisjunction
.....
353
What are acrocentric chromosomes
have centromeres near the ends
354
Robertsonian translocation
Acrocentric chromosomes fuse with loss of both short arms, can be balanced or unbalanced
355
Which chromosomes can undergo robertsonian translocation
paris 13, 14, 15, 21 and 22
356
What happens to the short arms in a robertsonian translocation
The reciprocal product is formed from the long armed chromosome but because they have useless genes they are usually lost quickly.
357
Cri-du-chat syndrome genetics
Congenital microdeletion of short arm of chrom. 5 (46,XX or XY, 5p-)
358
Cri-du-chat presentation
Microcephaly, moderate to severe MR, high-pitched crying/mewing, epicanthal folds, cardiac abnormalities (VSD)
359
Williams syndrome genetics
Congenital microdeletion of long arm of chrom. 7 (deleted region includes elastin gene)
360
Williams presentation
Elfin facies, MR, hypercalcemia (incr. sensitivity to vit. D), well developed verbal skills, extremely friendly, CV problems
361
What are the 22q11 deletion syndromes
DiGeorge and Velocardiofacial syndromes
362
CATCH-22
Cleft palate, abnormal facies, thymic aplasia, cardiac defects, hypocalcemia secondary to parathyroid aplasia, due to microdeletion at chromosome 22q11.
363
22q11 deletion path
Aberrant development of 3rd and 4th branchial pouches
364
DiGeorge syndrome presentation
thymic, parathyroid, and cardiac defects
365
Velocardiofacial syndrome
palate, facial, and cardiac defects
366
B1
thiamine (TPP)
367
B2
riboflavin (FAD,FMN)
368
B3
niacin: NAD+
369
B5
pantothenic acid (CoA)
370
B6
pyridoxine (PLP)
371
B7
biotin
372
B9
folate
373
B12
cobalamin
374
What B vitamins stored in liver
B12 and folate, the rest are peed out
375
B-complex deficiencies typical presentation
Dermatitis, glossitis, and diarrhea
376
Vitamin A is used as treatment for
Treats measles and AML, subtype M3. Retin-A for wrinkles and acne
377
Vitamin A phys
Antioxidant, visual pigments (retinal), normal differentiatino of epithelial cells into specialized tissue (pancreatic cells, mucus cells), prevents squamous metaplasia
378
Vit A Deficiency
Night blindness (nyctalopia); dry, scaly skin (xerosis cutis); alopecia; corneal degeneration (keratomalacia); immune suppression
379
Vit A Excess
Arthralgias, skin changes (scaly), alopecia, pseudotumor cerebri, cerebral edema, osteoporosis, hepatic abnormalities, teratogenic (cleft palate, cardiac abnormalities), so a negative preg. test and relaiable contraception are needed before isotretinoin is prescribed for severe acne
380
Thiamine function
Thiamine pyrophosphate (TPP): cofactor for several dehydrogenase enzyme reactions: pyruvate dehydrogenase, alpha-ketoglutarate dehydrogenase (TCA cycle), transketolase (HMP shunt), Branched chain ketoacid dehydrogenase
381
Thiamine mnemonic
ATP: alpha-ketoglutarate dehyd., transketolase, pyruvate dehydroganase ....and throw in branched chain ketoacid dehydrogenase
382
Thiamine deficiency presentation
Wernicke-Korsakoff: triad (confusion, ophthalmoplegia, ataxia); confabulation, personality change, memory loss (permanent).Ber1Ber1: Dry: polneuritis, symmetrical muscle wasting. Wet: high output cardiac failure (dilated cardiomyopathy), edema.
383
Wernicke-Korsakoff path
Damage to medial dorsal nucleus of the thalamus, mammillary bodies
384
Thiamine deficiency path
Impaired glucose breakdown, ATP depeltion worsened with glucose infusion; highly aerobic tissues (brain, heart) affected first.
385
Thiamine def. cause
Malnutrition and alcoholism
386
Thiamine def. diagnosis
Increased RBC transketolase activity following thiamine administration
387
Thiamine is what B vitamin
B1
388
Riboflavin function
Part of FAD and FMN, used as cofactors in redox reactions, e.g. succinate dehydrogenase reaction in the TCA cycle
389
Riboflavin deficiency
Cheilosis and Corneal vascularization (2 C's of B2)
390
Niacin function
NAD+, NADP+.
391
Niacin tx
dyslipidemia, lowers VLDL and raises HDL
392
Niacin synthesis
Need tryptophan, synthesis requires B2 and B6
393
Niacin deficiency
Glossitis. Severe is pellagra (caused by Hartnup disease and malignant carcinoid syndrome), and isoniazid.
394
Pellagra presentation
3 D's of B3: diarrhea, dementia, dermatitis
395
Dermatitis in pellagra
Casal necklace or hyperpigmentation of sun-exposed limbs
396
Tryptophan metabolism in Hartnup, carcinoid, and isoniazid
Hartnup: dec. trypt absorptionCarcinoid: Inc. trypt metabolismIsoniazid: decreased B6
397
Niacin excess
Facial flushing (prostaglandin, not histamine), hyperglycemia, hyperuricemia
398
Pantothenate function
Coenzyme A and fatty acid synthase
399
B5 is
"pento"thenate
400
Pantothenate deficiency
Dermatitis, enteritis, alopecia, adrenal insufficiency
401
Pyridoxine function
Converted to pyridoxal phosphate, used in transamination (ALT and AST), decarboxylation reactions, glycogen phosphorylase. Synthesis of cystathionine, heme, niacin, histamine, serotonin, epinephrine, norepinephrine, dopamine, and GABA
402
Pyridoxin deficiency
Convulsions, hyperirritability, peripheral neuropathy (isoniazid and oral contraceptives), sideroblastic anemias due to impaired hemoglobin synthesis and iron excess
403
Biotin Function
Cofactor for carboxylation enzymes (which add 1-carbon group)
404
Biotin mnemonic
Avidin in egg whites avidly binds biotin
405
Biotin reactions
Pyruvate carboxylaseAcetylCoA carboxylasePropionyl-CoA carboxylase
406
Biotin deficiency
Rare. Dermatitis, alopecia, enteritis. Caused by abx or excessive ingestion of raw egg whties
407
folate function
Turned into tetrahydrofolate for 1-carbon transfer/methylation reactions. Synthesizing nitogenous bases in DNA and RNA
408
Folate sources
Leafy green vegetables, absorbed in jejunum. Folate from Foliage.
409
Folate deficiency
macrocytic, megaloblastic anemia; hypersegmented PMNs, glossitis, no neurologic symptoms
410
folate def. labs
increased homocysteine, normal methylmalonic acid
411
folate def. in US
most common vit. deficiency, seen in alcoholics and pregnancy
412
folate def. causes
Phenytoin, sulfonamides, methotrexate
413
Cobalamin function
cofactor in homocysteine methyltransferase (transfers methyl groups as methylcobalamin) and methlmalonyl-CoA mtuase
414
Cobalamin deficiency
macrocytic, megaloblastic anemia; hypersegmented PMNs, paresthesias, subacute combined degeneration due to abnormal myelin
415
What is subacute combined denegeration
degeneration of dorsal columns, lateral corticospinal tracts, and spinocerebellar tracts.
416
Cobalamin blood work
elevated serum homocysteine and methylmalonic acid levels
417
Permanent effect of prolonged B12 deficiency
irreversible nerve damage
418
Cause of B12 deficiency
Only made by microorganisms, only from animal products. Veganism, malabsorption (Diphyllobothrium latum), lack of intrinsic factor (pernicious anemia, gastric bypass surgery), or absence of terminal ileum (Crohn's).
419
Diagnosis of pernicious anemia
Anti-intrinsic factor antibodies
420
Draw out reactions for B12 and B6
....
421
What are the B12 reactions
Homocysteine to Methionine via Homocysteine methyltransferase AND methylmanolyl-CoA to succinyl-CoA via methylmalonyl-CoA mtuase
422
What are the B6 reactions
Homocysteine to cysteine and Succinyl-CoA to Heme....but not all of them??
423
Folates (B9) reactions
Used in reaction from homocysteine to methionine but not in forming succinyl-CoA (which is used for myelin synthesis)
424
Vit C functions
helps iron absorption by reducing to Fe2+ stateHydroxylating proline and lysine in collagenNeeded for dopamine Beta-hydroxylase to convert DA to NE
425
Treatment for methemoglobinemia
Vit C is ancillary tx by reducing Fe3+ to Fe2+
426
Scurvy presentation
swollen gums, bruising, hemarthrosis, anemia, poor wound healing, perifollicular and subperiosteal hemorrhages, corkscrew hair, weakened immune systhem
427
Vit. C excess
N/V/D, fatigue, calcium oxalate kidney stones. Increased risk of iron toxicity for people who receive transfusions, hereditary hemochromatosis
428
D2
ergocalciferol: from plants
429
D3
cholecalciferol: milk, sun-exposed skin (stratum basale)
430
Vit D storage form
25-OHD3
431
Vit D active form
1,25-(OH)2D3 (calcitriol)
432
Vit D function
Inc. intestinal absorption of calcium and phosphate, inc. bone mineralization
433
Vit D def.
Rickets in kids, osteomalacia in adults, hypocalcemic tetany
434
Breastmilk and Vit D
Low in Vit D, breastfed babies need oral vitamin D
435
Vit D Excess
HyperCa, hypercalciuria, loss of appetite, stupor
436
Causes of Vit D excess
Sarcoid (inc. activation of vitamin D by epitheliod macrophages)
437
Vit E is also called
tocopherol and tocotrienol
438
Vit E function
Antioxidant (protects RBCs and membranes from free radical damage)
439
Vit E and blood thinners
Can enhance anticoagulation due to warfarin
440
Vit E Def.
hemolytic anemia, acanthocytosis, muscle weakness, posterior column and spinocerebellar tract demyelination
441
Vit E def. simply explained
Like B12, with no anemia, PMN changes, or increased serum methylmalonic acid levels
442
Vit K function
Cofactor for gamma-carboxylation of glutamate residues on proteins for blood clotting (II, VII, IX, X) and proteins C and S
443
Vit K def. presentation
Inc. PT and aPTT with normal bleeding time
444
Vit K def. causes
Neonates (no bacteria in gut), prolonged use of broad-spectrum antibiotics
445
Vit K and breast milk
Not in breast milk, neonates need an injection at birth
446
Zinc function
Essential for the activity of 100% enzymes. Zinc fingers (transcription factor motifs)
447
Zinc def.
Delayed wound healing, hypogonadism, less adult hair, dysgeusia, anosmia, acrodermatitis enteropathica, may predispose to alcoholic cirrhosis
448
What reactions happen in the mitochondria
Beta-oxidation, acetyl-CoA production, TCA cycle, Ox phos
449
What reactions happen in the cytoplasm
Glycolysis, fatty acid synthesis, HMP shunt, protein synthesis (RER), steroid synthesis (SER), cholesterol synthesis
450
What happens in both mitochondria and cytosol
Heme synthesis, Urea cycle, Gluconeogenesis (HUGs take two)
451
What is a phosphorylase
Adds phosphate without ATP (e.g. glycogen phosphorylase)
452
What is a carboxylase
Transfers CO2 groups with the help of biotin (e.g. pyruvate carboxylase)
453
Mutase does
relocates a functional group within a molecule
454
Know what type of enzyme specific ones are??
????
455
What cofactor is needed for ethanol metabolism
NAD+ (turned into NADH)
456
limiting reagent in ethanol metabolism
NAD+
457
Kinetics of alcohol metabolism
zero-order kinetics
458
NADH/NAD+ ratio in alcohol metabolism
Increases in liver
459
What is the effect of the NADH/NAD+ ratio on pyruvate, oxaloacetate, and glyceraldehyde-3-phosphate
Lactate, malate and glycerol-3-phosphate
460
Fomepizole
Inhibits alcohol dehydrogenase (used to treat methanol or ethylene glycol poisoning)
461
Disulfiram
Inhibits acetaldehyde dehydrogenase (acetaldehyde accumulates, contributing to hangover sxs)
462
Elevated NADH/NAD+ prevents TCA production of NADH causing increased utilization of acetyl-CoA for ketogenesis (ketoacidosis) and lipogenesis (hepatosteatosis)
....
463
Kwashiorkor....
.....
464
Kwashiorkor
Protein malnutrition! Skin lesions, edema, liver malfunction (fatty change due to dec. apolipoprotein synthesis). Small child with swollen belly.
465
Kwashiorkor mnemonic
MEAL: Malnutrition (protein), Edema, Anemia, Liver (fatty)
466
Marasmus
Total calorie malnutrition resulting in tissue and muscle wasting, loss of SubQ fat, and variable edema
467
How much net ATP via malate-aspartate shuttle
32. because NADH is used in cytosol and matrix so you don't lose anything.
468
Net ATP via glycerol-3-phosphate shuttle
30. because you end up with reduced FADH2, so you end up losing 2 ATP per glucose (2.5(NADH)-1.5(FADH2)=1 (the loss of energy from one pyruvate formed)
469
Malate-aspartate shuttle
Needed because NADH can't cross the inner mitochondrial membrane. In cytosol OAA is converted to malate and this then enters matrix to produce a new NADH in the TCA cycle. Aspartate is the way OAA can move from matrix to cytosol.
470
Glycerol-3-phosphate shuttle
DHAP formed in glycolysis is reduced to glycerol-3-phosphate which is then oxidized by glycerol-3-phosphate dehydrogenase which gives its electrons to FADH2, hence the loss. It also is a way of regenerating NAD+ for glycolysis.
471
Glycolysis net ATP production
2 net
472
Arsenic effect
Causes glycolysis to produce 0 net ATP
473
What does CoA and lipoamide carry
Acyl groups
474
What does Biotin carry
COOH (carboxylic acid group)
475
What does THFs carry
1-carbon units
476
What does SAM carry
Methyl (CH3) groups
477
What does TPP carry
Aldehydes
478
What family of molecules in NAD+ and NADP+
Nicotinamides from vitamin B3 (Niacin)
479
What family is FAD+
Flavins (Riboflavin B2)
480
NAD+ for what general reactions
Catabolic (for energy production)
481
NADPH+ for what general reactions
Anabolic processes (steroid and fatty acid synthesis), Respiratory burst, Cytochrome P-450 systemGlutathione reductase
482
First step of glycogen synthesis in the liver?
Glucose to glucose-6-phosphate
483
Know all the differences between Hexokinase vs. Glucokinase...
Location, Km, Vmax, Induced by Insulin, Feedback-inhibited by glucose-6-P, gene mutation associated with maturity onset diabetes of the young (MODY)
484
What does it mean that hexokinase is feedback-inhibited by glucose6P
Excess glucose-6-P will stop hexokinase which makes sense in muscles where you only use the pathways to make energy. In liver, you'll have excess glucose-6-P but you don't want to slow it down so it does not feedback-inhibit.
485
What is MODY
Aut. dom. gene disrupting insulin production. (monogenic diabetes) Type I and Type II are multigenic
486
What does phosphofructosekinase-1 reaction do
Fructose-6-P to Fructose-1,6-bisphosphate
487
What reactions in glycolysis produce ATP?
1,3-BPG to 3-PG by phosphoglycerate kinase ANDPhosphoenolpyruvate to pyruvate by Pyruvate Kinase
488
Why does fructose-2,6-BP induce PFK-1?
Because when glucose is in high supply it is produced by PFK-2 and activates PFK-1
489
Why does alanine slow down pyruvate kinase?
alanine is made from pyruvate so if you have too much alanine, you probably have a lot of pyruvate, hence pyruvate kinase not needed.
490
Know regulation by F2,6BP
.....
491
Are Fructose bisphosphatase-1 and PFK-1 the same enzyme with different phosphorylations too?
No. They are not the same. PFK-1 reaction is unidirectional.
492
Where is pyruvate dehydrogenase complex and what does it do?
it is mitochondrial and links glycolysis to TCA cycle
493
When is PDH active?
In fed state
494
PDH has how many enzymes
3
495
Name the PDH cofactors
1. Pyrophosphate (B1, thiamine; TPP)2. FAD (B2, riboflavin)3. NAD (B3, niacin)4. CoA (B5, pantothenate)5. Lipoic acid
496
What activates PDH
Exercise which also increases Ca2+, ADP, and NAD+/NADH ratio which all increase PDH
497
What is the basic reaction for PDF
pyruvate+NAD+ +CoA leads to acetyl-CoA+CO2+NADH
498
PDH is like what TCA cycle complex
alpha-ketoglutarate dehydrogenase complex (same cofactors, simlar substrate and action)
499
Arsenic does what to PDH
Inhibits lipoic acid
500
Arsenic presentation
Vomiting, rice-water stools, garlic breath
