Biochem from Matt Flashcards
(433 cards)
1
Q
What are the components of a histone?
A
2 each of: H2A, H2B, H3, H4
2
Q
What is the role of H1 in histones?
A
Ties nucleosome beads together
3
Q
Which chromatin protein is not part of the nucleosome core?
A
H1
4
Q
Which form of chromatin is condensed and inactive?
A
Heterochromatin
5
Q
Which form of chromatin is open and transcribed?
A
Euchromatin
6
Q
Histone methylation effects
A
Usually blocks DNA transcription (can activate it in some contexts)
7
Q
Histone acetylation effects
A
Relaxes DNA coiling, allows transcription
8
Q
What amino acids are histones rich in?
A
Lysine and arginine (basic, bind negatively-charged DNA)
9
Q
Name the purines
A
AdenineGuanine
10
Q
Name the pyrimidines
A
CUT: cytosine, uracil, thymine
11
Q
What chemical group does guanine have?
A
Ketone
12
Q
What chemical group does thymine have?
A
THYmine has a meTHYl
13
Q
How many hydrogen bonds in G-C pairs? A-T pairs? Significance?
A
GC = 3, AT = 2. Higher GC content = higher melting temperature.
14
Q
What amino acids are necessary for purine synthesis?
A
GAG: glycine, aspartate, glutamine
15
Q
What are the components of a nucleoside?
A
Base + ribose (sugar)
16
Q
What are the components of a nucleotide?
A
Base + ribose (sugar) + phosphate
17
Q
Group involved in purine synthesis
A
N10-formyl-tetrahydrofolate
18
Q
Orotic aciduria defect
A
UMP synthase (AR)
19
Q
Orotic aciduria findings
A
Orotic acid in urine, megaloblastic anemia (does not improve with B12 administration), no hyperammonemia
20
Q
Orotic aciduria treatment
A
Oral uridine administration
21
Q
What converts ribonucleotides to deoxyribonucleotides? What inhibits this enzyme?
A
Ribonucleotide reductaseHydroxyurea
22
Q
6-mercaptopurine
A
Blocks de novo purine synthesis6-MP, prodrug is azathioprine
23
Q
5-FU
A
Blocks thymidylate synthase (finding: low dTMP)
24
Q
Methotrexate (MTX)/Trimetoprim (TMP)
A
Block dihydrofolate reductase (finding: low dTMP)TMP inhibits bacterial enzyme
25
What two pathways use carbamoyl phosphate?
1) De novo pyrimidine synthesis2) Urea cycle
26
Adenosine deaminase deficiency pathophysiology
Excess ATP and dATP inhibit ribonucleotide reductase (negative feedback) and prevent DNA synthesis. Autosomal recessive.
27
Lesch-Nyhan syndrome defect
HGPRT (He's Got Purine Recovery Trouble)
Hyperuricemia, Gout, Pissed off (aggression, self-mutilation), Retardation (intellectual disability), dysTonia (choreoathestosis)
Converts hypoxanthine to IMP and guanine to GMPX-linked recessive.
28
What does degenerate/redundant refer to (genetic code)?
Most amino acids are coded for by multiple codons (exceptions: Met and Trp)
29
What does unambiguous refer to (genetic code)?
Each codon specifies 1 amino acid
30
What does commaless/overlapping refer to (genetic code)?
Read continuously from a fixed starting point
31
What does universal refer to (genetic code)?
Conserved throughout evolution (exception: mitochondria)
32
Adenosine deaminase deficiency findings
Low lymphocyte count (SCID)
33
Lesch-Nyhan syndrome findings
Excess uric acid (hyperuricemia and gout) and de novo purine synthesis Retardation, self-mutilation, aggression, choreoathetosisHGPRT: (Hyperuricemia, Gout, Pissed off (aggression, self-mutilation,) Retardation, dysTonia)
34
Adenosine deaminase deficiency treatment
Gene therapy
35
Silent DNA mutation
Same AA, base change is usually in the third position (tRNA wobble allows this)
36
Missense DNA mutation
Changed AA (conservative = similar properties in new AA - like hydrophobic for hydrophobic)
37
Nonsense DNA mutation
Early stop codon
38
Frameshift DNA mutation
Insertion or deletion results in misreading of all downstream codons
39
Rank the types of mutations: frameshift, missense, silent, nonsense
Silent < missense < nonsense < frameshift
40
What breaks down dopamine, norepi, and epi?
MAO and COMT
41
Breakdown product of dopamine?
HVA
42
Breakdown product of epinephrine?
Metanephrine
43
Breakdown product of norephinephrine?
VMA, normetanephrine
44
Catecholamine synthesis progression
Phe -> Tyr -> Dopa -> Dopamine -> Norepi -> Epi
45
What converts phenylalanine to tyrosine? What cofactor is required?
Phenylalanine hydroxylaseNADPH and THB (NADPH converts DHB to THB)
46
What converts tyrosine to dopa? What cofactor is required?
Tyrosine hydroxylaseNADPH and THB (NADPH converts DHB to THB)
47
What converts dopa to dopamine? What cofactor is required?
Dopa decarboxylaseVit. B6
48
What converts dopamine to norepinephrine? What cofactor is required?
Dopamine beta-hydroxylaseVit. C
49
What converts norepinephrine to epinephrine? What cofactor is required?
PNMTSAM
50
What does a hydroxylase do?
Adds an -OH group
51
What does a decarboxylase do?
Removes COOH
52
PKU defect
Phe hydroxylase or THB cofactor (malignant)Autosomal recessiveTyrosine becomes an essential AA
53
PKU findings
Phenylketones in urine (phenylacetate, phenyllactate, phenylpyruvate)Mental retardation, growth retardation, seizures, fair skin, eczema, musty body odor
54
PKU treatment
Restrict Phe in diet (present in aspartame-containing products) and increase Tyr intake
55
Maternal PKU
Lack of proper dietary therapy during pregnancyFindings in infant: microcephaly, mental retardation, growth retardation, congenital heart defects
56
Alkaptonuria (ochronosis) defect
Homogentisic acid oxidase in the degrade pathway of tyrosine to fumarateAutosomal recessive
57
Alkaptonuria (ochronosis) findings
Dark connective tissue, brown sclera, urine turns black on prolonged exposure to air. May have debilitating arthralgia (homogentisic acid is toxic to cartilage).
58
Albinism defect
Tyrosinase (can't make melanin from Tyr) Autosomal recessiveTyrosine transporters (less tyrosine available)Also can result from lack of migration from neural crest cells
59
Albinism findings
Increased risk of skin cancer (lack of melanin)
60
Homocystinuria defects (3 forms)
Cystationine synthase deficiencyLow affinity of cystathionine synthase for pyridoxal phosphateHomocysteine methyltransferase deficiency (All three are autosome recessive)
61
Homocystinuria findings
Excess homocysteine in urineCysteine becomes an essential AAMental retardation, osteoporosis, tall stature, kyphosis, lens subluxation (downward and inward), atherosclerosis (stroke and MI)
62
Homocystinuria treatment
Cystathionine synthase deficiency: restrict Met intake, increase Cys, B12, and folate intake in dietLow affinity cystathionine synthase: B6 in dietHomocysteine methyltransferase: B12
63
Cystinuria defect
Renal tubular AA transporter for Cys, ornithine, Lys, and Arg in the PCT of the kidneysAutosomal recessive
64
Cystinuria findings
Excess cysteine in urinePrecipitation of hexagonal crystals and renal staghorn calculi
65
Cystinuria treatment
Hydration and urinary alkalinization
66
Maple syrup urine disease defect
Blocked degradation of branched amino acids (Ile, Leu, Val - I Love Vermont maple syrup) due to low alpha-ketoacid dehydrogenase (B1)Autosomal recessive
67
Maple syrup urine disease findings
Urine smells like syrupIncreased alpha-ketoacids in the blood, especially LeuSevere CNS defects, mental retardation, and death
68
Hartnup disease defect
Defective neutral amino acid transporter on renal cells and intestinal epithelial cells
69
Hartnup disease findings
Tryptophan excretion in urine and decreased absorption from gutLeads to pellagra (niacin deficiency)
70
Glycogen bond types
Linkages: alpha-1,4Branches: alpha-1,6
71
Insulin receptor type
Tyrosine kinase
72
Glucagon receptor type
GPCR
73
Glycogen regulation by insulin
Activates protein phosphatases which inactivate glycogen phosphorylase and glycogen phosphorylase kinase (glycogenesis)
74
Glycogen regulation by glucagon/epinephrine
Activate PKA, which activates glycogen phosphorylase kinase, which activates glycogen phosphorylase (glycogenolysis)
75
Glycogen regulation by Ca++/calmodulin
Activates glycogen phosphorylase kinase so that glycogenolysis is coordinated with muscle activity
76
Glycogenolysis progression (skeletal muscle)
Glycogen -> glucose-1-phosphate -> glucose-6-phosphate -> used in glycolysis
77
Glycogenolysis progression (liver)
Glycogen -> glucose-1-phosphate -> glucose-6-phosphate -[glucose-6-phosphatase]-> glucose released into blood
78
What converts glucose-1-phosphate to UDP-glucose?
UDP-glucose phosphorylase
79
What converts UDP-glucose to glycogen?
Glycogen synthase
80
What adds branches to glycogen?
Branching enzyme
81
What releases glucose-1-phosphate from glycogen?
Glycogen phosphorylaseDefect in McArdle's (type V)
82
What takes branches off of glycogen?
Debranching enzyme (alpha-1,6-glucosidase)Defect in Cori's disease (type III)
83
Type I glycogen storage disease defect
Glucose-6-phosphataseAutosomal recessiveVon Gierke's disease
84
Type II glycogen storage disease defect
Lysosomal alpha-1,4-glucosidase Autosomal recessivePompe's disease
85
Type III glycogen storage disease defect
Debranching enzyme (alpha-1,6-glucosidase)Autosomal recessiveCori's disease
86
Type V glycogen storage disease defect
Skeletal muscle glycogen phosphorylaseMcArdle's disease
87
Type I glycogen storage disease findings
Severe fasting hypoglycemiaHigh glycogen in liver, high blood lactate, hepatomegalyVon Gierke's disease
88
Type II glycogen storage disease findings
Cardiomegaly and systemic findings leading to early deathPompe's trashes the Pump (heart, liver, muscle)
89
Type III glycogen storage disease findings
Like type I (fasting hypoglycemia, high glycogen in liver, hepatomegaly) but with normal blood lactateGluconeogenesis is intactCori's disease
90
Type V glycogen storage disease findings
High glycogen in muscle that can't be broken down leads to painful cramps and myoglobinuria with exerciseMcArdle's = Muscle
91
What breaks down glycogen in lysosomes?
Alpha-1,4-glucosidaseDefect in Pompe's disease (type II)
92
Fabry's disease deficit
Alpha-galactosidase AX-linked recessive(Lysosomal storage disease)
93
Fabry's disease findings
Peripheral neuropathy of hands/feet, angiokeratomas, cardiovascular/renal diseaseCeramide trihexosidase accumulates(Lysosomal storage disease)
94
Gaucher's disease deficit
GlucocerebrosidaseAutosomal recessive(Lysosomal storage disease)
95
Gaucher's disease findings
Most common lysosomal storage diseaseHepatosplenomegaly, aseptic necrosis of femur, bone crises, Gaucher's cells (macrophages that look like crumpled tissue paper)Glucocerebroside accumulates
96
Niemann-Pick disease deficit
SpingomyelinaseAutosomal recessive(Lysosomal storage disease)No man picks (Niemann-Pick) his nose with his sphinger (shingomyelinase)
97
Niemann-Pick disease findings
Progressive neurodegeneration, hepatosplenomegaly, cherry-red spot on macula, foam cellsSphingomyelin accumulates(Lysosomal storage disease)
98
Tay-Sachs disease deficit
Hexosaminidase AAutosomal recessive(Lysosomal storage disease)Tay-SaX lacks heXosaminidase
99
Tay-Sachs disease findings
Progressive neurodegeneration, developmental delay, cherry-red spot on macula, lysosomes with onion skin, no hepatosplenomegaly (vs. Niemann-Pick)GM2 ganglioside accumulates(Lysosomal storage disease)
100
Krabbe's disease deficit
GalactocerebrosideAutosomal recessive(Lysosomal storage disease)
101
Krabbe's disease findings
Peripheral neuropathy, developmental delay, optic atrophy, globoid cellsGalactocerebroside accumulates(Lysosomal storage disease)
102
Metachromatic leukodystrophy deficit
Arylsulfatase AAutosomal recessive(Lysosomal storage disease)
103
Metachromatic leukodystrophy findings
Central and peripheral demyelination with ataxia, dementiaCerebroside sulfate accumulates(Lysosomal storage disease)
104
Hurler's syndrome deficit
Alpha-L-iduronidaseAutosomal recessive(Lysosomal storage disease)
105
Hurler's syndrome findings
Developmental delay, gargoylism, airway obstruction, corneal clouding, hepatosplenomegalyHeparan sulfate and dermatan sulfate accumulate(Lysosomal storage disease)
106
Hunter's syndrome deficit
Iduronate sulfataseX-linked recessive(Lysosomal storage disease)Hunters see clearly (no corneal clouding) and aim for the X (X-linked)
107
Hunter's syndrome findings
Mild Hurler's (developmental delay, gargoylism, airway obstruction, corneal clouding, hepatosplenomegaly) + aggressive behavior, no corneal cloudingHeparan sulfate and dermatan sulfate accumulate(Lysosomal storage disease)Hunters see clearly (no corneal clouding) and aim for the X (X-linked)
108
Carnitine deficiency: pathophysiology and signs
Inability to transport LCFA's into the mitochondria, results in toxic accumulationWeakness, hypotonia, hypoketotic hypoglycemia
109
Citrate shuttle pathway
Fatty acid synthesisSYtrate = SYnthesis
110
Carnitine shuttle pathway
Fatty acid degradationCARnitine = CARnage of fatty acids
111
Acyl-CoA dehydrogenase deficiency signs
Acyl-CoA dehydrogenase does the first step in beta-oxidation (degradation) of fatty acidsDeficiency gives you increased dicarboxylic acids, decreased glucose and ketones
112
When might the body make ketone bodies?
Prolonged starvation (low glucose), diabetic ketoacidosis (low glucose utilization), alcoholism (excess NADH)
113
How many calories are in a gram of protein? Carbohydrate? Fat?
Protein and carbohydrate: 4 kcalFat: 9 kcal
114
What are two examples of ketone bodies?
Acetoacetate and beta-hydroxybutyrate
115
Why does alcoholism lead to ketone body production?
Excess NADH shunts oxaloacetate to malate, which stalls the TCA cycle, shunting glucose and FFA toward ketone body production
116
What are clinical signs of ketone body production?
Breath smells like acetone (fruity)Urine tests for ketones (exception: doesn't detect beta-hydroxybutyrate)
117
Cholesterol synthesis: rate-limiting step
HMG-CoA reductase converts HMG-CoA to mevalonateInhibited by statins
118
What happens to cholesterol after synthesis?
2/3 of plasma cholesterol is esterified by lecithin-cholesterol acyltransferase (LCAT)
119
Main energy supply in the fed state (after a meal)
Glycolysis and aerobic respirationInsulin stimulates storage of lipids, proteins, and glycogen
120
Main energy supply in the fasting state
Hepatic glycogenolysis (major), hepatic gluconeogenesis, adipose release of FFAGlucagon and adrenaline stimulate use of fuel reserves
121
Main energy supply in the starvation state (days 1-3)
Hepatic glycogenolysis, adipose release of FFA, muscle and liver shift fuel use from glucose to FFA, hepatic gluconeogenesis from peripheral tissue lactate and alanine, and from adipose tissue glycerol and propionyl-CoA (only odd-chained FFA)Glycogen reserves depleted after day 1, RBCs can't use ketones (no mitochondria)
122
Main energy supply in the starvation state (days 3+)
Adipose stores (ketone bodies become the main energy source for brain and heart), protein degradation acceleratesAmount of adipose storage determines survival time
123
Order of energy stores used in exercise
Stored ATP (initial) --> creatine phosphate (seconds) --> anaerobic glycolysis (minutes) --> aerobic metabolism and FA oxdation (hours)
124
Type IV glycogen storage disease defect
Branching enzymeAutosomal recessiveAndersen's disease
125
Type IV glycogen storage disease findings
Long unbranched glycogen, cirrhosis, early deathAndersen's disease
126
Pancreatic lipase actions
Degrades dietary TG in small intestine
127
Lipoprotein lipase (LPL) actions
Degrades TG circulating in chylomicrons and VLDLs
128
Hepatic TG lipase (HL) actions
Degradation of TG remaining in IDL
129
Hormone-sensitive lipase actions
Degradation of TG stored in adipocytes
130
Lecithin-cholesterol acyltransferase (LCAT) actions
Esterification of cholesterol (adds esters to make nascent HDL into mature HDL)
131
Cholesterol ester transfer protein (CETP) actions
Transfer of cholesterol esters to other lipoprotein particles (from mature HDL to VLDL, IDL, LDL)
132
Rank these lipoproteins from most dense to least dense: LDL, IDL, VLDL, HDL, chylomicron
HDL > IDL > LDL > VLDL > chylomicron
133
Lipid transport in blood overview
Chylomicrons synthesized in intestine from dietary fat and released into bloodLPL pulls off FFA's which get taken up by cells for energy, leaving behind chylomicron remnants which get taken up by the liver Liver produces and releases VLDL, LPL removes TGs from VLDL, producing IDL and then HL removes TGs to yield LDL, which gets taken up by the liverNascent HDL is produced and secreted by the liver and intestine, matures when LCAT adds esters
134
ApoE function + what lipoproteins have it?
Mediates remnant uptake by liverAll except LDL
135
ApoA-I function + what lipoproteins have it?
Activates LCATHDL
136
ApoC-II function + what lipoproteins have it?
LPL cofactorChylomicrons, VLDL, HDL
137
ApoB-48 function + what lipoproteins have it?
Mediates chylomicron secretionChylomicrons, remnants,
138
ApoB-100 function + what lipoproteins have it?
Binds LDL receptorVLDL, IDL, LDL
139
LDL functions
Transports cholesterol from liver to tissuesFormed by HL modification of IDL in the periphery Taken up by receptor-mediated endocytosis (clathrin) LDL is Lousy ("bad" cholesterol)
140
HDL functions
Transports cholesterol from periphery to liver (reverse transport)Repository for ApoC and ApoE (needed for chylomicron and VLDL metabolism)Secreted by liver and intestineHDL is Healthy ("good" cholesterol)
141
Chylomicron functions
Delivers dietary TGs to peripheral tissue, delivers cholesterol to liver in the form of chylomicron remnants (depleted of TAGs)Secreted by intestine
142
VLDL functions
Delivers hepatic TGs to peripheral tissueSecreted by liver
143
IDL functions
Delivers triglycerides and cholesterol to the liverFormed by VLDL degradation in the periphery
144
Hyperchylomicronemia (type I): increased blood level?
Chylomicrons, TG, cholesterol
145
Familial hypercholesterolemia (type IIa): increased blood level?
LDL, cholesterol
146
Hypertryiglyceridemia (type IV): increased blood level?
VLDL, TG
147
Abetalipoproteinemia defect
Microsomal triglyceride transport protein (MTP) defectAutosomal recessiveLow B-48 and B-100 -> low chylomicron and VLDL synthesis and secretion
148
Hyperchylomicronemia (type I): pathophysiology?
Autosomal recessiveLPL deficiency or altered ApoC-IIPancreatitis, hepatosplenomegaly, eruptive/pruritic xanthomas (no additional atherosclerosis risk)
149
Familial hypercholesterolemia (type IIa): pathophysiology?
Autosomal dominantLDL receptor defectAccelerated atherolsclerosis, tendon xanthomas, corneal arcus (white, gray, or blue ring)
150
Hypertryiglyceridemia (type IV): pathophysiology?
Autosomal dominantHepatic overproduction of VLDLPancreatitis
151
Microsomal triglyceride transport protein (MTP) functions
Important in lipoprotein assembly and secretion, requires B-48 and B-100Defect in abetalipoproteinemia
152
Abetalipoproteinemia findings
Symptoms appear in the first few months of lifeLipid accumulation within enterocytes in intestines (inability to export absorbed chylomicrons) Failure to thrive, steatorrhea, acanthoyctosis, ataxia, night blindness
153
Origin of replication
Consensus sequence of base pairs in genome where DNA replication begins
154
Replication fork
Y-shaped region along DNA template where leading and lagging strands are synthesized
155
Helicase
Unwinds DNA at the replication fork
156
Single-stranded binding proteins
Prevent strands from reannealing
157
DNA topoisomerases (what antibiotic blocks them?)
Creates a nick in the helix to relieve supercoiling created during replicationFluoroquinolones (-floxacin) inhibit DNA gyrase
158
Primase
Makes an RNA primer on which DNA polymerase III can initiate replication
159
DNA polymerase III
Prokaryotic only. 5' -> 3' synthesis, 3' -> 5' proofreading (exonuclease)
160
DNA polymerase I
Prokaryotic only. 5' -> 3' synthesis, 5' -> 3' exonuclease (to degrade RNA primer)
161
DNA ligase
Forms phosphodiesterase bonds within a strand of dsDNA (joins Okazaki fragments)
162
Telomerase
Adds DNA to 3' ends to avoid loss of genetic material with duplication
163
Nucleotide excision repair
Repairs bulky helix-distorting lesions (multiple bases)Endonucleases release the damaged bases, DNA polymerase and ligase fill in the gapDefect in xeroderma pigmentosum (pyrimidine dimers following UV light exposure)
164
Base excision repair
Glycosylases recognize and remove single bases, apurinic/apyrimidinic endonuclease cuts DNA, empty sugar is removed, gap is filled and sealedImportant for spontaneous deamination repair
165
Mismatch repair
Newly synthesized strand is recognized, mismatched nucleotides are removed, gap is filled and resealedMutated in hereditary nonpolyposis colorectal cancer (HNPCC) - autosomal dominant
166
Nonhomologous end joining
Brings together two ends of DNA fragments to repair double-stranded breaks (no homology requirement)Defect in ataxia telangiectasia
167
What direction are DNA and RNA synthesized in?
5' -> 3'
168
What direction are proteins synthesized in?
N-terminus to C-terminus (C is the caboose)
169
What reaction happens when you add another base to DNA or RNA?
Triphosphate bond of the incoming nucleotide is attacked by the 3'-OH of the last base on the existing chainDrugs that block DNA synthesis (also used in lab a lot) have no 3'-OH so chain terminates
170
3 types of RNA
rRNA (most abundant) - ribosomes, protein synthesismRNA (longest) - transcription producttRNA (smallest) - carry charged AA's to ribosome
171
mRNA start codon
AUG (rarely GUG)AUG inAUGurates protein synthesis
172
What AA does AUG code for in eukaryotes?
Methionine
173
What AA does AUG code for in prokaryotes?
f-Met (formyl-methionine)
174
mRNA stop codons
UAA, UGA, UAGU Are AnnoyingU Go AwayU Are Gone
175
What base number is the transcription start point
+1
176
Promoter function, location, effect of mutation
Site where RNA polymerase and other transcription factors bind to DNA Upstream of gene locus, TATA and CAAT boxesMutations result in dramatic reduction in gene transcription
177
Enhancer function, location
Activates gene expression by binding transcription factorsCan be close to, far from, or within the gene it regulates
178
Silencer function, location
Inactivates gene expression by binding negative regulators (repressors)Can be close to, far from, or within the gene it regulates
179
RNA polymerase I
Makes rRNA
180
RNA polymerase II
Makes mRNA
181
RNA polymerase III
Markes tRNA
182
What inhibits RNA polymerase II? What happens if you ingest it?
Alpha-amanitin from death cap mushroomsCauses severe hepatotoxicity if ingested
183
Prokaryotic RNA polymerase
Only one, makes all 3 kinds of RNA (r, m, t)
184
RNA processing: initial transcript name
hnRNA (heterogeneous nuclear RNA)If destined for translated, pre-mRNA
185
RNA processing steps
Addition of 5' cap (addition of 7-methylguanosine cap) and 3' polyadenylationSplicing
186
Polyadenylation signal
AAUAAA
187
Splicing steps (+ what component might lupus patients make antibodies against?)
1) Primary transcript combines with snRNPs to form the spliceosome2) Lariat-shaped (looped) intermediate is generated3) Lariat is released to remove the intron and join two exonsLupus patients can have snRNP antibodies
188
Are introns or exons expressed into protein?
Exons
189
tRNA structure (+ what is the 3' sequence?)
75-90 nucleotides, cloverleaf form with secondary structure and anticodon opposite of the 3' end3' sequence is CCA: Can Carry Amino acids
190
tRNA charging enzyme
Aminoacyl-tRNA synthetase
191
tRNA wobble
Accurate base pairing often only required for the first 2 nucleotidesCodons differing in the 3rd position frequently code for the same AA (degeneracy)
192
What makes sure the write AA charges a tRNA?
Aminoacyl-tRNA synthetase reads the amino acid before and after it binds the tRNA. Hydrolyzes bond if incorrect.
193
What antibiotic binds the 30S ribosome and prevents the attachment of aminoacyl-tRNA to the ribosome?
Tetracyclines (-cyclines)
194
Posttranslational modificiations: trimming
Removal of N- or C-terminal pro peptides from zymogens
195
Posttranslational modificiations: covalent alterations
Phosphorylation, glycosylation, hydroxylation, methylation, acetylation
196
Posttranslational modificiations: proteasomal degradation
Attachment of ubiquitin to target them for breakdown
197
Eukaryotic ribosome components
40S + 60S = 80S
198
Prokaryotic ribosome components
30S + 50S = 70S
199
Protein synthesis initiation
Initiation factors (eIF's) help assemble the 40S ribosomal subunit with the initiator tRNA and are released when the mRNA and the ribosomal subunit assemble with the complex
200
What molecule provides the energy for tRNA charging?
ATP
201
What molecule provides the energy for AA translocation?
GTP
202
Protein synthesis elongation
1) Aminoacyl-tRNA binds to the A site (except initiator Met, which binds the P site)2) rRNA catalyzes peptide bond formation, transfers growing peptide to AA in the A site3) Ribosome advances 3 nucleotides toward the 3' end of the mRNA, pushing peptidyl tRNA to the P site (translocation)
203
Protein synthesis elongation
Stop codon is recognized by release factor, completed protein is released from the ribosome
204
Ribosome sites: A, P, E
A: incoming Aminoacyl-tRNAP: accommodates the growing PeptideE: holds Empty tRNA as it Exits
205
What antibiotic binds the 30S subunit to inhibit formation of the initiation complex?
Aminoglycosides (-micin or -mycin, though azithromycin and vancomycin and others are exceptions)
206
What antibiotic binds the 50S subunit and inhibits peptidyl transferase activity?
Chloramphenicol
207
What antibiotic binds 50S subunit and prevents release of uncharged tRNA from the E site?
Macrolides (azithromycin, erythromycin, other -mycins)
208
What phase of the cell cycle do Rb and p53 function in?
Prevent the transition from G1 to S phase
209
Permanent cell cycle characteristics + examples
Remain G0Neurons, skeletal muscle, cardiac muscle, RBCs
210
Stable (quiescent) cell cycle characteristics + examples
Enter G1 from G0 when stimulatedHepatocytes, lymphocytes
211
Labile cell cycle characteristics + examples
Never go to G0, divide rapidly with a short G1Bone marrow, gut epithelium, skin, hair follicles, germ cells
212
RER functions
Synthesis of secretory proteins and N-linked oligosaccharide addition to proteins
213
Nissl bodies
RER in neurons, synthesize enzymes and peptide neurotransmitters (like ACh)
214
Free ribosomes
Synthesis of cytosolic and organeller proteins
215
Cell types rich in RER
Mucus-secreting goblet cells of the small intesting and antibody-secreting plasma cells
216
Cell types rich in SER
Liver hepatocytes and steroid hormone-producing cells in the adrenal cortex
217
Cell cycle phases
Interphase (G1, S, G2) and metaphase (Prophase, Metaphase, Anaphase, Telophase) + G0
218
Peroxisome functions
Membrane-enclosed, catabolism of very long fatty acids and AAs
219
Proteasome functions
Barrel-shaped protein complex that degrades proteins tagged with ubiquitin
220
Clathrin vesicles
Golgi -> lysosomes, plasma membrane -> endosomes (receptor-mediated endocytosis)
221
COPI vesicles
Retrograde golgi -> golgi, golgi -> ER
222
COPII vesicles
Anterograde golgi -> golgi, ER -> golgi
223
I-cell disease defect
Failure of addition of mannose-6-phosphate to lysosome proteins (get secreted outside of cell instead of targeted to lysosome)
224
I-cell disease findings
Coarse facial features, clouded corneas, restricted joint movement, high plasma levels of lysosomal enzymesFatal in childhood
225
Golgi apparatus function
Trafficking center
226
What amino acid(s) are modified with N-oligosaccarharides?
Asparagine
227
What amino acid(s) are modified with O-oligosaccharides?
Serine and threonine
228
Microtubule components
Polymerized dimers of alpha-tubulin and beta-tubulin (each dimer has 2 GTP bound)
229
What structures are made of microtubules?
Flagella (eukaryotic), cilia, mitotic spindles, axonal trafficking
230
Dynein motor direction
Retrograde (+ -> -)
231
Kinesin motor direction
Anterograde (- -> +)Kinesin Keeps going forward
232
Chediak-Higashi syndrome defect
Mutation in lysosomal trafficking regulator gene (LYST), which is required for microtubule-dependent sorting of endosomal proteins into late endosomes
233
Chediak-Higashi findings
Recurrent pyogenic infections, partial albinism, peripheral neuropathy
234
Drugs that act on microtubules
Mebendazole/thiabendazole (antihelminthic)Griseofulvin (antifungal)Vincristine/vinblastine (chemo)Paclitaxel (breast cancer)Colchicine (gout)Microtubules Get Constructed Very Poorly
235
Cilia structure
9 + 2 arrangement of microtubules with dyne in arms on the outer doublets
236
Kartagener's syndrome defect
Dynein arm defect
237
Kartagener's syndrome findings
Male infertility (immotile sperm) and reduced female fertility, bronchiectasis, recurrent sinusitis, situs inversus (congenital inversion of organs)
238
Connective tissue IHC intermediate filament stain
Vimentin
239
Muscle IHC intermediate filament stain
Desmin
240
Epithelial cell IHC intermediate filament stain
Cytokeratin
241
Neuroglia IHC intermediate filament stain
GFAP
242
Neruonal IHC intermediate filament stain
Neurofilaments
243
Plasma membrane composition
Asymmetric lipid bilayer composed of cholesterol (adds fluidity), phospholipids, sphingolipids, glycolipids, proteins
244
Intermediate filaments function
Structural
245
Microtubule function
Movement
246
Actin and myosin function
Microvilli, muscle contraction, cytokinesis, adherens junctions
247
Collagen type I
Most commonBone, skin, tendonDefect in osteogenesis imperfecta
248
Collagen type II
Cartilage, vitreous body, nucleus pulposusType II: car-two-lage
249
Collagen type III
Reticulin - skin, blood vessels, uterus, fetal tissue, granulation tissueDefective in vascular type Ehlers-Danlos (threE D)
250
Collagen type IV
Basement membraneDefect in Alport syndrome
251
What does ouabain inhibit?
Na-K ATPaseLeads to indirect inhibition of Na/Ca exchange, which increases intracellular Ca and contractility
252
What do cardiac glycosides inhibit?
Na-K ATPaseLeads to indirect inhibition of Na/Ca exchange, which increases intracellular Ca and contractility
253
What does the Na/K ATPase exchange?
3 Na+ go out, 2 K+ come in
254
Collagen mnemonic
Be So Totally (I) Cool (II), Read (III) Books (IV)
255
Collagen synthesis steps: overview
1) synthesis (RER), 2) hydroxylation (ER), 3) glycosylation (ER), 4) exocytosis, 5) proteolytic processing (extracellular), 6) cross-linking (extracellular)
256
Collagen synthesis steps: synthesis
Translation of collagen alpha chains (preprocollagen) - usually Gly-X-Y (X and Y are proline or lysine)RER
257
Collagen synthesis steps: hydroxylation
Hydroxylation of specific proline and lysine residuesRequires Vit. C (deficiency = scurvy)ER
258
Collagen synthesis steps: glycosylation
Glycosylation of pro-alpha-chain hydroxylysine residues and formation of procollagen via hydrogen and disulfide bonds (triple helix of 3 collagen alpha chains)Problems with this = osteogenesis imperfectaER
259
Collagen synthesis steps: exocytosis
Exocytosis into extraceullar space
260
Collagen synthesis steps: proteolytic processing
Cleavage of disulfide-rich terminal regions of procollagenProduces insoluble tropocollagen
261
Collagen synthesis steps: cross-linking
Reinforcement of staggered tropocollagen molecules via covalent lysine-hydroxylysine cross-linkage Lysyl oxidase, requires Cu+2Problems with this = Ehlers-Danlos
262
Osteogenesis imperfecta: most common defect
Abnormal type I collagenAutosomal dominant
263
Osteogenesis imperfecta: findings
Fractures with minimal trauma (including during birth), blue sclerae (due to translucency of connective tissue), hearing loss, dental imperfections
264
Ehlers-Danlos findings
Hyperextensible skin, tendency to bleed and bruise easily, hyper mobile joints6 types, inheritance and severity vary, can be autosomal recessive or dominantCan be associated with joint dislocation, berry aneurysms, organ rupture
265
Alport syndrome defect
Abnormal type IV collagenX-linked recessive
266
Elastin
Stretchy protein within skin, lungs, larger arteries, elastic ligaments, vocal cords, ligament flavaRich in proline and glycine (nonhydroxylated)Broken down by elastase, which is inhibited by A1AT
267
Polymerase chain reaction (PCR)
Used to amplify a specific DNA fragmentSteps: 1) denaturation (hot), 2) annealing (cool), 3) elongation (hot)Uses DNA polymerase from heat-stable bacteria (Taq)Run samples out on agarose gels (smaller runs father)
268
Fibrillin
Scaffold for elastase formation
269
Elastase findings in emphysema
In congenital emphysema (A1AT deficiency), you get excess elastase activity (less elastin)
270
Alport syndrome findings
Progressive hereditary nephritis and deafnessOcular disturbancesType IV collagen is important in kidney, ears, and eyes
271
Southern blot
DNASNoW DRoP
272
Northern blot
RNASNoW DRoP
273
Western blot
ProteinSNoW DRoP
274
Southwestern blot
DNA-binding proteinsSNoW DRoP
275
Microarray
Stick nucleic acid sequences to a slide, prepare labeled DNA or RNA probes and hybridize them to the slide, compare binding between samplesUsed to profile expression in a ton of genes at onceCan detect SNPs
276
ELISA (enzyme-linked immunosorbent assay)
Tests for antibody-antigen reactivityDetermine if a particular antibody or antigen is present in a sample (HIV antibody is an example)
277
Indirect ELISA
Uses a test antigen to see if a specific antibody is present in a patient's sample
278
Direct ELISA
Uses a test antibody to see if a specific antigen is present in the patient sample
279
FISH (fluorescence in situ hybridization)
Fluorescent DNA or RNA probe binds to a specific geneUsed for specific localization of genes and direct visualization of anomalies (things that are too small to be seen by karyotping)Fluorescence = gene is present because probe can bind
280
Cloning methods
1) isolate mRNA, 2) use reverse transcriptase to generate a cDNA (lacks introns!), 3) insert cDNA fragments into plasmids with antibiotic resistance genes (so you can select for these colonies in culture), 4) transform the plasmids into bacteria, 5) grow bacteria on antibiotic-containing medium to generate a cDNA library
281
Gene expression modifications
Knock-outs and Knock-ins (either through random insertion or targeted homologous recombination0Cre-lox: useful for studying genes that are necessary for embryonic development - can knock them out in adulthood with tamoxifenRNAi: dsRNA separates and promotes degradation and silencing of a specific mRNA
282
Karyotyping
Metaphase chromosomes are stained, matched up, and numberedUsed to diagnose chromosome imbalances
283
Codominance (+ example)
Both alleles contribute to the phenotypeBlood type AB
284
Variable expressivity (+ example)
Phenotype varies among individuals with the same genotypePatients with NF1 have varying disease severity
285
Incomplete penetrance (+ example)
Not all individuals with a mutant genotype end up showing the mutant phenotypeNot everyone with BRCA1 mutations get breast cancer
286
Pleiotropy (+ example)
One gene contributes to multiple phenotypesPKU causes many symptoms ranging from retardation to hair changes
287
Imprinting (+ example)
Differences in expression depending on whether the mutation is maternal or paternalPrader-Willi and Angelman's syndrome - 15(q11-13)
288
Anticipation (+ example)
Increased severity or earlier onset in succeeding generationsHuntington's disease
289
Loss of heterozygosity (+ example)
A patient with a mutation in a tumor suppressor gene requires the second allele to be mutated before cancer develops (NOT true with proto-oncogenes)Retinoblastoma, MEN I
290
Dominant negative mutation (+ example)
In a heterozygote, the mutant allele produces a product that prevents the normal produce from functioningA transcription factor that can still bind DNA but has a mutation in its allosteric site (so normal signals don't pull it off) that prevents the normal transcription factor from binding
291
Linkage disequilibrium
Tendency for certain alleles at linked loci to occur together more often than chanceIndicates genes are close together on the chromosome
292
Mosaicism (+ example)
Cells in the body differ in genetic makeup due to post-fertilization loss or change. Can be germ-line and produce disease that is not carried in parent's somatic cellsMcCune-Albright is lethal if somatic but survivable if mosaic
293
Locus heterogeneity (+ example)
Mutations at different loci produce the same phenotypevHL disease and MEN 2B both cause pheochromocytomas
294
Heteroplasmy
Prescence of both normal and mutated mitochondrial DNA resulting in variable expression of mitochondrially-inherited diseases
295
Allelic heterogeneity (+ example)
Mutations within one gene can produce the same phenotypeMultiple mutations of the CFTR gene can give CF like symptoms
296
Uniparental disomy (+ example)
Offspring receives 2 copies of a chromosome from one parent and no copies from the other parentUniparental is eUploid, not aneuploidConsider in a parent with a recessive disorder and only one affected parent
297
Hardy-Weinberg equation
p^2 + 2pq + q^2 = 1p + q = 1p^2 = frequency of homozygosity for pq^2 = frequency of homozygosity for q2pq = frequency of heterozygosity
298
Imprinting
At some loci, only one allele is active and the other is inactive (imprinted, inactivated by methylation)Disease can occur from deletion of the active allele or from uniparental disomy
299
Prader-Willi syndrome imprinting
Paternal allele is not expressed
300
Prader-Willi findings
Mental retardation, hyperphagia, obesity, hypogonadism, hypotonia
301
Angelman's syndrome imprinting
Maternal allele is not expressed
302
Angelman's findings
Mental retardation, seizures, ataxia, inappropriate laughter
303
When does the error occur in heterodisomy?
Meiosis I
304
When does the error occur in isodisomy?
Meiosis II
305
Hardy-Weinberg differences with X-linked genes
Frequency of a recessive disease in males = q, in females = q^2
306
Mitochondrial inheritance disease
Often present with myopathy and CNS diseaseMuscle biopsy shows ragged red fibers
307
Autosomal dominant pedigree characteristics
Multiple generations, both male and females affected
308
Autosomal recessive pedigree characteristics
Often only seen in one generation, both parents have to be carriers but likely not affectedEnzyme deficiencies
309
X-linked recessive pedigree characteristics
Sons of heterozygous mothers get 50% of diseaseNo male-to-male transmission
310
X-linked dominant pedigree characteristics
Transmitted through both parentsAll female offspring of an affected father are affected
311
Mitochondrial inheritance pedigree characteristics
Transmitted only through mother, all offspring of affected females have the disease
312
Hypophosphatemic rickets
Vit. D-resistant RicketsIncreased phosphate wasting at the proximal tubuleX-linked dominant
313
Achondroplasia defect
FGF receptor 3Autosomal dominant
314
Autosomal-dominant polycystic kidney disease (ADPKD) defect
PKD1 (vs. PKHD1 for AR childhood form)Chromosome 16 (16 letters in "polycystic kidney")Autosomal dominant
315
Familial adenomatous polyposis defect
APC geneChromosome 5 (5 letters in "polyp")Autosomal dominant
316
Familial hypercholesterolemia (hyperlipidemia type IIA) defect
LDL receptorAutosomal dominant
317
Hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu syndrome) defect
Disorder of blood vessels resulting in abnormal formation and weakened vasculature (more bleeding)Autosomal dominant
318
Hereditary spherocytosis defect
Spectrin or ankyrin defectAutosomal dominant
319
Huntington's disease defect
Trinucleotide repeat (CAG)Chromosome 4 (HUNTING 4 food)Autosomal dominant
320
Marfan's syndrome defect
Fibrillin-1 Results in abnormal elastaseAutosomal dominant
321
Multiple endocrine neoplasias (MEN) defect
MEN1 - menin (tumor suppressor)Autosomal dominant (loss of heterozygosity)MEN2A/B - RET (proto-oncogene)Autosomal dominant
322
Neurofibromatosis type I (von Recklinghausen's disease) defect
Gene on chromosome 17(17 letters in "von Recklinhausen")Autosomal dominant
323
Neurofibromatosis type II defect
NF2 gene on chromosome 22(type 2 is 22)Autosomal dominant
324
Tuberous sclerosis defect
TSC geneAutosomal dominant
325
von Hippel-Lindau disease defect
VHL deletion results in constitutive expression of HIF (transcription factor)Chromosome 3 (3 letters in v H L)Autosomal dominant
326
Achondroplasia findings
Dwarfism, short limbs, large head, normal trunk sizeAssociated with advanced paternal age
327
Autosomal-dominant polycystic kidney disease (ADPKD) findings
Bilateral, massive enlargement of kidneys due to multiple large cystsFlank pain, hematuria, hypertension, progressive renal failure, polycystic liver disease, berry aneurysms, mitral valve prolapseInfantile form is recessive
328
Familial adenomatous polyposis findings
Colon becomes covered with adenomatous polyps after pubertyProgresses to colon cancer unless resected
329
Familial hypercholesterolemia (hyperlipidemia type IIA) findings
Elevated LDLHeterozygotes: 300 level cholesterolHomozygotes: 700+ level cholesterolAtherosclerotic disease early in life, tendon xanthomas, MI and stroke
330
Hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu syndrome) findings
Telangiectasia, recurrent epistaxis, skin discolorations, arteriovenous malformations (AVMs)
331
Hereditary spherocytosis findings (+ treatment)
Spheroid erythrocytes, hemolytic anemia, increased MCHC (mean corpuscular hemoglobin concentration)Splenectomy is curative
332
Huntington's disease findings
Depression, progressive dementia, choreiform movements, caudate atrophy, lower levels of GABA and AChAppears between 20 and 50 (anticipation is a factor)
333
Marfan's syndrome findings
Tall with long extremities, pectus excavatum, hypermobile joints, long and tapering fingers and toes (arachnodactyly), cystic medial necrosis of aorta which can lead to incompetence and dissecting aortic aneurysms, floppy mitral valve, subluxation of lenses
334
NF type I (von Recklinghausen's disease) findings
Cafe-au-lait spots, neural tumors, Lisch nodules (pigmented iris hamartomas), skeletal disorders (scoliosis) and optic pathway gliomas
335
NF type II findings
Bilateral acoustic schwannomas, juvenile cataracts
336
Tuberous sclerosis findings
Facial lesions (adenoma sebaceum), hypopigmented "ash leaf spots," cortical and retinal hamartomas, seizures, mental retardation, renal cysts and angiomyolipmas, cardiac rhabdomyomas, astrocytomasIncomplete penetrance, variable presentation
337
von Hippel-Lindau findings
Hemangioblastomas of retina/cerebellum/medulla, bilateral renal cell carcinoma, pheochromocytoma
338
Albinism inheritance pattern
Autosomal recessive
339
Autosomal recessive polycystic kidney disease: inheritance pattern and defect
Autosomal recessivePKHD1 (vs. PKD1 for the AD adult form)
340
Cystic fibrosis defect
CFTR on chromosome 7 (Phe 508 is most common)Mutation causes abnormal protein folding, resulting in degradation of channel in the ER (never reaches cell surface)Apical Cl- channel expressed in the lungs, GI trace, vas deferensAutosomal recessive
341
Cystic fibrosis pathophysiology
CFTR secretes Cl- in lungs and GI tract and reabsorbs Cl- in sweat glandsMutant protein gets retained in RER and not transported to cell membraneAbnormal Cl- secretion causes less H2O secretion and compensatory Na+ reabsorption via epithelial Na+ channels, which causes H2O reabsorption Abnormally thick mucus secreted into lungs and GI tract.Na+ reabsorption also causes more negative transepithelial potential difference
342
Cystic fibrosis findings
Infertility in males (bilateral absence of vas deferens), fat-soluble vitamin deficiencies and steatorrhea, bronchiectasis, pancreatic insufficiency, nasal polyps, meconium ileus in newborns, failure to thrive in infancy is possible
343
Cystic fibrosis diagnosis
High Cl- concentration in sweat testAlkalosis and hypokalemia because ECF water and Na+ losses lead to renal K+/H+ wasting
344
Cystic fibrosis infections
Recurrent pulmonary infections from Pseudomonas aeruginosa and S. aureus
345
List X-linked recessive disorders
Bruton's agammaglobulinemia, Wiskott-Aldrich syndrome, Fabry's disease, G6PD deficiency, Ocular albinism, Lesch-Nyhan syndrome, Duchenne's (and Becker's) muscular dystrophy, Hunter's syndrome, Hemophilia A and B, Ornithine transcarbamoylase (OTC) deficiency"Be Wise, Fool's GOLD Heeds Silly HOpe"
346
Duchenne's muscular dystrophy defect
X-linked frameshift mutationDeletion of dystrophin gene leads to accelerated muscle breakdown. Normally anchors muscle fibers in skeletal and cardiac muscle to alpha- and beta-dystroglycan (ECM proteins) -> myonecrosisDuchenne's = Deleted DystrophinDMD is the longest gene, which predisposes it to higher rates of mutation
347
Duchenne's muscular dystrophy findings
Weakness beginning in the pelvic girdle and progressing superiorly, pseudohypertrophy of calves (muscle replaced by fat), cardiac myopathy, Gower's maneuver (using your arms to stand up)Starts before age 5
348
Becker's muscular dystrophy defect
X-linked frameshift mutationDeletion of dystrophin gene leads to accelerated muscle breakdown. Normally anchors muscle fibers in skeletal and cardiac muscleLess severe than Duchenne's
349
Becker's muscular dystrophy findings
Similar to Duchenne's (pelvic girdle weakness, pseudohypertrophy of calves, cardiac myopathy, Gower's maneuver) but less severeOnset in adolescence or early adulthood
350
Fragile X syndrome defect
X-linked defect affecting the methylation and expression of the FMR1 gene(CGG)n repeat
351
Fragile X syndrome findings
Macroorchidism (enlarged testes), long face with a large jaw, large everted ears, autism, mitral valve prolapseFragile X = eXtra large testes, jaws, ears2nd most common genetic
352
List trinucleotide repeat expansion diseases
Huntington's disease (CAG), myotonic dystrophy (CTG), Friedrich's ataxia (GAA), fragile X syndrome (CGG)
353
Lesch-Nyhan treatment
Allopurinol and febuxostatXanthine oxidase inhibitors
354
Down syndrome defect
Trisomy 2195% Meiotic nondisjunction, 4% Robertsonian translocation, 1% mosaicismMost common viable chromosomal disorder and most common genetic mental retardation
355
Down syndrome clinical findings
Mental retardation, flat facies, prominent epicanthal folds, simian crease, gap between 1st two toes, duodenal atresia, congenital heart disease (ostium primum-type ASD)Associated with ALL (acute lymphoblastic leukemia) and Alzheimer's disease
356
Down syndrome pregnancy quad screen and US results
Up: beta-hCG, inhibin ADown: alpha-fetoprotein, estriolUS: increased nuchal translucency
357
Edwards' syndrome defect
Trisomy 18
358
Edwards' syndrome clinical findings
Severe mental retardation, rocker-bottom feet (also in Patau's), micrognathia (small jaw), low-set ears, clenched hands, prominent occiput, congenital heart diseaseDeath usually occurs within 1 yearEdwards': Ears
359
Edwards' syndrome quad screen
Up: noneDown: alpha-fetoprotein, beta-hCG, estriolNormal: inhibin A
360
Patau's syndrome defect
Trisomy 13
361
Patau's syndrome clinical findings
Severe mental retardation, rocker-bottom feet (also in Edwards), microphtalmia, microcephaly, cleft lip/palate, holoprosencephaly, polydactyly, congenital heart diseaseDeath usually occurs within 1 yearPatau's: liP/Palate, holoProsencephaly, Polydactyly
362
Patau's syndrome quad screen and US results
Up: noneDown: free b-HCG, PAPPA-AUS: increased nuchal translucency
363
Robertsonian translocation
Nonreciprocal chromosomal translocation commonly involving 13, 14, 15, 21, 22 (acrocentric, have short arms)Long arms from two chromosomes fuse at the centromere, short arms are lostCan result in miscarriage, stillbirth, and chromosomal imbalance (trisomies)Balanced translocations are often normal
364
Down syndrome age of presentation
21 (Drinking age for Down)
365
Edwards' syndrome age of presentation
18 (Election age for Edwards')
366
Patau's syndrome age of presentation
13 (Puberty for Patau's)
367
Cri-du-chat syndrome defect
Microdeletion of short arm of chromosome 5 (46XX, 5p- or 46XY, 5p-)
368
Cri-du-chat findings
Microcephaly, mental retardation, high-pitched crying/mewing, epicentral folds, cardiac abnormalities (VSD)Cri du chat = cry of the cat (mewing)
369
Williams syndrome defect
Microdeletion of the long arm of chromosome 7 (includes elastin)
370
Williams syndrome findings
Distinctive "elfin" facies, intellectual disability, hypercalcemia (sensitive to vit. D), well-developed verbal skills and extreme friendliness, CV problems
371
22q11 deletion syndrome findings
CATCH-22: Cleft palate, Abnormal facies, Thymic hyperplasia (t-cell deficiency), Cardiac defects, Hypocalcemia secondary to parathyroid aplasia due to microdeletion at 22q11
372
22q11 deletion syndrome defect
Microdeletion of 22q11 due to aberrant development of 3rd and 4th branchial pouches
373
DiGeorge syndrome
22q11 deletion syndromeThymic, parathyroid, and cardiac defects
374
Velocardiofacial syndrome
Palate, facial, and cardiac defects
375
Methylation of CpG islands
Blocks transcription
376
Fat-soluble vitamins
KADE
377
Water-soluble vitamins
B (1-12) and C
378
Vit. A function
Antioxidant, constituent of visual pigments (retinal), essential for normal differentiation of epithelial cells into specialized tissue (pancreatic cells and mucus-secreting cells), prevent squamous metaplasia
379
Vit. A deficiency
Night blindness, dry scaly skin (xerosis cutis), alopecia, corneal degeneration (keratomalacia), immune suppression
380
Vit. A excess
Arthralgia, fatigue, headache, skin changes, sore throat, alopecia, cerebral edema, pseudotumor cerebri (high intracranial pressure in the absence of a tumor), osteoporosisTeratogenic (cleft plate and cardiac abnormalities): people going on isotretinoin for severe acne need to take a pregnancy test and be on contraception
381
Is toxicity from fat-soluble or water-soluble vitamins more common? Why?
Fat-soluble: accumulate in fat, difficult to wash away
382
What causes fat-soluble vitamin deficiencies?
Malabsorption syndromes (steatorrhea), such as CF or sprueMineral oil intake is also a possible cause
383
What conditions can give you B-complex deficiencies?
Dermatitis, glossitis, diarrhea
384
Which B vitamins are stored in the liver?
B12 (cobalamin) and folate (B9)
385
Vit. B1 function
Cofactor (TPP - thiamine pyrophosphate) for enzymes that do decarboxylation reactions (dehydrogenases - pyruvate (links glycolysis to TCA cycle), alpha-ketoglutare (TCA cycle), branched chain AA and transketolase (HMP shunt))Alpha-ketoglutarate DH, Transketolase, and Pyruvate DH required for ATP synthesis
386
Vit. B1 deficiency (+ causes)
Impaired glucose breakdown (ATP depletion), worsened by glucose infusion. Brain and heart affected firstWernicke-Korsakoff, beriberiCaused by malnutrition and alcoholism
387
Wernicke-Korsakoff findings
Confusion, ophthalmoplegia, ataxia, confabulation, personality change, memory loss
388
Dry beriberi findings
Polyneuritis, symmetrical muscle wasting
389
Wet beriberi findings
High-output heart failure (dilated cardiomyopathy), edema
390
Where is Vit. A found?
Liver and leafy vegetables
391
What can Vit. A be used to treat?
Wrinkles, acne, measles, AML (subtype M3)
392
Vit. A other name
Retinol"retin-A"
393
Vit. B1 other name
Thiamine
394
Glutamate derivatives (+ cofactor required)
GABA and glutathioneB6
395
Arginine derivatives
Creatinine, urea, NO
396
Glycine derivatives (+ cofactor required)
Porphyrin and hemeB6
397
Histidine derivatives (+ cofactor required)
HistamineB6
398
Tryptophan derivatives (+ cofactor required)
Two pathwaysNiacin and NAD+/NADP+ require B6Serotonin and melatonin require BH4
399
Ornithine transcarbamoylase deficiency (OTC) defect
OTC geneX-linked recessiveInterferes with ability to eliminate ammonia, excess carbamoyl phosphate gets converted to orotic acid
400
Ornithine transcarbamoylase deficiency (OTC) findings
Increased orotic acid in blood and urine, low BUN, hyperammonemia symptomsNo megaloblastic annemia (vs. orotic aciduria)
401
Hyperammonemia causes
Can be acquired liver disease or hereditary urea cycle defects
402
Hyperammonemia pathophysiology
Excess NH4+ depletes alpha-ketoglutarate, leading to inhibition of the TCA cycle
403
Hyperammonemia symptoms
Tremor (asterixis), slurring of speech, somnolence, vomiting, cerebral edema, blurring of vision
404
Hyperammonemia treatment
Limit protein in dietBenzoate or phenylbutyrate (bind AAs and lead to exertion)Lactulose acidifies the GI tract and traps NH4+ for excretion
405
What form of AA is present in proteins?
L-form
406
Essential AAs
Glucogenic: Met, Val, HisGlucogenic/ketogenic: Ile, Phe, Thr, TrpKetogenic: Leu, LysNeed to be supplied in the diet
407
Acidic AAs
Aspartate and Glutamate Negatively charged at body pH
408
Basic AAs
Arginine (most basic), Lysine, HistidineArg and Lys are positively-charged at body pH, Histidine has no charge
409
Urea cycle metabolites
Ornithine + carbamoyl phosphate -> citrulline + aspartate -> arginosuccinate -> arginine - fumarate (fumarate leaves cycle) -> ureaOrdinarily, Careless Cats Are Also Frivolous About Urination
410
What is the urea cycle for?
Degradation of excess nitrogen (NH4+) generated during amino acid catbalosim
411
What amino acids are involved in ammonium transport?
Alanine and glutamate
412
What metabolite couples to NH3 from amino acids? Where does this occur?
alpha-Ketolglutarate (also part of the TCA cycle)Muscle
413
What transports NH3 from the muscle to the liver?
Alanine cycle
414
What is the Cori cycle?
Lactate produced in lactic acid fermentation (anaerobic fermentation) is transported to the liver and converted to glucose
415
Pyrimethamine
Blocks dihydrofolate reductase (finding: low dTMP)
416
Leflunomide
Blocks dihydroorotate dehydrogenase (carbamoyl phosphate -> orotic acid conversion)
417
Mycophenolate
Inhibit IMP dehydrogenaseRibavirin does the same thing
418
Ribavirin
Inhibit IMP dehydrogenaseMycophenolate does the same thing
419
Chaperone proteins
Facilitate protein foldingIn yeast, some are heat-shock proteins expressed at high temperatures to prevent denaturing
420
CDKs
Cyclin-dependent kinases, constitutive and inactive alone
421
Cyclins
Regulatory proteins that control cell cycle events, phase specific, activate CDKs
422
Cyclin-CDK complexes
Must be both activated and inactivated for cell cycle to progress
423
Signal recognition particle (SRP) (+ what happens when it is dysfunctional)
Abundant cytosolic ribonucleoprotein that traffics proteins from the ribosome to the RERWhen absent, proteins accumulate in the cytosol
424
What can osteogenesis imperfecta be confused with?
Child abuse
425
Menkes disease defect
Connective tissue disease caused impaired copper absorption and transportLeads to decreased lysyl oxidase activity (requires Cu++)
426
Menkes disease findings
Brittle "kinky" hair, growth retardation, hypotonia
427
Lysyl oxidase: function, cofactor
Extracellular tropocollagen cross-linkageRequires Cu++
428
Hardy-Weinberg law assumptions
No mutations, no natural selection, completely random mating, no net migration of individuals
429
Cystic fibrosis treatment
N-acetylcysteine to loosen mucus plugs (cleaves disulfide bonds within mucus glycoproteins)Dornase alfa (DNAse) to clear leukocytic debris
430
Myotonic type I muscular dystrophy
Finish this card
431
N-acetylglutamate deficiency findings
Hyperammonemia with high ornithine and normal urea cycle enzymes
432
N-acetylglutamate deficiency defect
Required cofactor for carbamoyl phosphate synthetase IAbsence leads to hyperammonemia
433
Start at B2
Page 91-105 left to finish
