Biochem Flashcards
1
Q
histone methylation / acetylation
A
methylation - inactivates transcription
acetylation - relaxes coiling allowing for transcription
2
Q
orotic aciduria
A
cant convert orotic acid into UMP (pyrimidine synth) due to defect in UMP synthase. AR inheritance
orotic acid in urine, megaloblastic anemia, failure to thrive
tx w/ oral uridine
3
Q
adenosine deaminase def
A
excess ATP / dATP > feedback inhibition > dec DNA synth > dec lymphocyte count
Major cause of SCID **
AR inheritance
4
Q
Lesch-Nyhan syndrome
A
absence of HGPRT (purine salvage) > excess uric acid production and de novo purine synth
x linked recessive
retardation, self mutilation, aggression, hyperuricemia, gout, choreoathetosis
5
Q
direction of DNA synth, RNA synth, mRNA reading, protein synth
A
DNA synth: 5’ > 3’
RNA synth: 5’ > 3’
mRNA reading: 5’ > 3’
protein synth: N > C terminus
6
Q
start codon
A
AUG
7
Q
ribosomal subunits for eukaryotes and prokaryotes
A
eu: 40S + 60S > 80S (even)
pro: 30S + 50S > 70S (odd)
8
Q
abx that block protein synth by binding to ribosomal subunits
A
aminoglycosides - 30s
tetracyclines - 30s
chloramphenicol - 50s
macrolides - 50s
9
Q
p53 and hypophosphorlyated Rb usually do what in cell cycle?
A
inhibit G1 to S progression
10
Q
mannose 6 phosphate is signal for transport to
A
lysosome
11
Q
inclusion cell disease
A
inherited lysosomal storage disorder, failure to add mannose 6 phosphate to lysosomal proteins
coarse facial features, cloudy corneas, restricted joint mvmt, high plasma levels of lysosomal enzymes. often fatal in childhood
12
Q
what kind of transport are COPI, COPII and clathrin used in, respectively?
A
COPI - retrograde
COPII - anterograde
clathrin - golgi > lysosome and PM > endosome
13
Q
Chediak Higashi syndrome
A
mutation in LYST (lysosomal trafficking regulator gene) > can’t do MT assisted sorting of endosomal proteins into late endosomes
recurrent pyogenic infections + partial albinism + peripheral neuropathy
14
Q
Kartagener’s syndrome
A
immotile cilia due to dynein arm defect
male infertility, female dec fertility, bronchiectasis, recurrent sinusitis, assoc w/ situs inversus
15
Q
defect in type I collagen is what disease?
A
osteogenesis imperfecta
16
Q
defect in type IV collagen is what disease?
A
alport syndrome
17
Q
scurvy happens b/c vitamin C is needed for what process?
A
synth of collagen (hydroxylation of proline and lysine)
18
Q
Ehlers Danlos is due to a defect in what step of collagen synthesis?
A
cross linking (extracellular)
19
Q
osteogenesis imperfecta
A
abnormal type I collagen (usually AD)
multiple fractures w/ minimal trauma, blue sclera, hearing loss, dental imperfections
20
Q
alport syndrome
A
abnormal type 4 collagen (XLR)
progressive nephritis and hearing loss, ocular disturbances
21
Q
alpha 1 antitrypsin
A
blocks elastase from breaking down elastin
deficiency can result in emphysema
22
Q
Southwestern blot
A
identifies DNA binding proteins
23
Q
imprinting
A
differences in gene expression depend on whether mutation is of maternal or paternal origin
ex - prader-willi and angelman’s syndromes
24
Q
dominant negative mutation
A
heterozygote produces nonfunctional protein that also prevents normal gene product from functioning
25
heteroplasmy
presence of both normal and mutated mtDNA resulting in variable expression in mitochondrial inherited disease
26
Hardy Weinberg eqn
p^2 + 2pq + q^2 = 1
27
in Prader-Willi and Angelman's syndromes, which parent's allele is not expressed, respectively?
Prader Willi - paternal not expressed
| Angelman's - maternal not expressed
28
example of x linked dominant disease
Hypophosphatemic rickets
29
hypophosphatemic rickets
x linked dominant disorder
| inc phosphate wasting in proximal tubule > rickets like presentation that does not respond to vit D
30
"ragged red fibers" on muscle biopsy
mitochondrial myopathy usually
31
achondroplasia mutated protein
FGF receptor 3
32
familial adenomatous polyposis mutated gene
APC gene
33
Osler Weber Rendu syndrome is also known as
hereditary hemorrhagic telangiectasia
34
NT changes in huntington's
dec GABA and ACh in brain
35
marfan's syndrome mutated gene
fibrillin-1
36
von Recklinhausen's dz aka...
NF type 1
37
Lisch nodules
pigmented iris hamartomas seen in NF type 1
38
NF type 2 findings
bilateral acoustic schwannomas, juvenile cataracts
39
Tuberous sclerosis findings and inheritance type
```
AD (incomplete penetrance)
facial lesions (adenoma sebaceum), ash leaf spots on skin, cortical and retinal hamartomas, seizures, mental retardation, renal cysts and angiomyolipomas, cardiac rhabdomyomas, astrocytomas
```
40
von hippel lindau findings
hemangioblastomas of retina/cerebellum/medulla, mult bilat renal cell carcinomas, other tumors
41
CF gene mutated
CFTR
42
mutated gene in duchenne's and becker's
dystrophin
43
Gower's maneuver assoc w/
Duchenne's muscular dystrophy
44
lab test to dx muscular dystrophies
inc CPK
45
fragile x mutated gene
FMR1 gene
46
top 2 MCC genetic mental retardation
Down syndrome
| Fragile X
47
genetic disorder assoc w/ macroorchidism
fragile x
48
4 trinucleotide repeat disease
huntington's - CAG
myotonic dystrophy - CTG
friedreich's ataxia - GAA
fragile x syndrome - CGG
49
congenital heart dz in Down syndrome
ostium primum ASD
50
pregnancy screening for Down syndrome
dec alpha fetoprotein, inc beta HCG, dec estriol, inc inhibin A
ultrasound - inc nuchal translucency in 1st TM
51
Edward's syndrome - genetic cause
trisomy 18
52
Edward's syndrome findings
mental retardation, rocker bottom feet, micrognathia, low set ears, clenched hands, prominent occiput, congenital heart dz
death within first year of life usually
53
pregnancy screening for Edward's syndrome
dec alpha fetoprotein, dec beta HCG, dec estriol, nl inhibin A
54
Patau's syndrome - genetic cause
trisomy 13
55
Patau's syndrome findings
severe mental retardation, rocker bottom feet, microphthalmia, microcephaly, cleft palate/lip, holoprosencephaly, polydactyly, congenital heart dz
death w/in first year of life usually
56
pregnancy screening for Patau's syndrome
dec beta HCG, dec PAPP-A, inc nuchal translucency
57
Cri du chat syndrome genetic cause
microdeletion of short arm of chromosome 5
58
Cri du chat syndrome findings
microcephaly, mental retardation, high pitched crying/mewing, epicanthal folds, ventricular septal defect
59
Williams syndrome genetic cause
microdeletion of long arm of chromosome 7
60
Williams syndrome findings
elfin facies, intellectual disability, hypercalcemia, good verbal skills, friendly w/ strangers, CV problems
61
2 22q11 deletion syndromes
Digeorge syndrome and velocardiofacial syndrome
62
22q11 deletion syndrome findings
cleft palate, abnl facies, thymic aplasia, cardiac defects, hypocalcema 2/2 PTH aplasia
63
vit A def
night blindness and dry skin
64
vit A excess
arthralgia, fatigue, HA, skin changes, sore throat, alopecia, teratogenic
65
3 syndromes assoc w/ B1 def
Wernicke-Korsakoff
wet beriberi
dry beriberi
66
vit B1 is needed for...
breakdown of glucose / production of ATP
67
classic triad of Wernicke-Korsakoff syndrome
confusion, ophthalmoplegia, ataxia
68
dry beriberi
b1 def
| polyneuritis, symmetrical muscle wasting
69
wet beriberi
high output cardiac failure, edema
70
vit b2 function
oxidation and reduction
71
vit B2 def
cheilitis and corneal vascularization
72
vit B3 is a constituent of what important metab molecule?
NAD (NAD derived from Niacin)
73
vit b3 def
pellagra: 3 D's of B3
| diarrhea, dermatitis, dementia
74
vit B5 is component of what metab molecule?
CoA
75
vit b5 def
dermatitis, enteritis, alopecia, adrenal insufficiency
76
fn of vit b6
transamination and decarboxylation rxns
| synth of heme, histamine, NTs
77
vit b6 def
peripheral neuropathy and siderblastic anemia
78
vit b9 is aka
folate!!
79
folate is vit...
b9
80
folate fn
synth of nitrogenous bases for DNA and RNA
81
folate def
macrocytic, megaloblastic anemia, neural tube defects in first TM
82
most common vit def in US
b9 (folate)
83
vit b12 def
macrocytic megaloblastic anemia, hypersegmented PMNs, neuro sx - paresthesia, subacute combined systems degeneration
84
s-adenosyl-methionine (SAM) is required for
converting NE to epi by donating methyl group
85
fns of vit C
antioxidant
keeps Fe in reduced state for absorption
hydroxylation of proline and lysine in collagen synth
cofactor for conversion of DA to NE
86
fn of vit D
inc intestinal abs of Ca and PO4, inc bone mineralization
87
vit D deficiency
Rickets in kids, osteomalacia in adults
| hypocalcemic tetany
88
vit E function
antioxidant that protects Erythrocytes
89
zinc def
delayed wound healing, hypogonadism, dec adult hair, dysgeusia, anosmia
90
limiting reagent in alcohol metabolism
NAD+
91
fomepizole
inhib alcohol dehydrogenase to protect from methanol or ethylene glycol poisoning
92
kwashiorkor
protein malnutrition > skin lesions, edema, fatty change in liver
93
marasmus
energy malnutrition > muscle wasting, loss of subq fat, variable edema
94
3 metab processes that occur in both cytoplasm and mitochondria
heme synth
urea cycle
gluconeogenesis
95
biotin (b7) is needed for
carboxylase enzymes to work
96
net ATP from aerobic vs anaerobic metab of glucose
aerobic - 32
| anaerobic - 2
97
NADPH is product of
HMP shunt
98
NADPH used in (4)
anabolic processes
respiratory burst
P450
glutathione reductase
99
hexokinase vs glucokinase
both start glycolysis (or glycogen synth in liver)
hexo - in most tissues, high affinity, low capacity, no change w/ insulin
gluco - in liver and beta cells of pancreas, low affinity, high capacity, induced by insulin
100
rate limiting enzyme of glycolysis
phosphofructokinase 1
101
2 enzyme/steps that req ATP and 2 that produce in glycolysis
require atp: hexokinase/glucokinase, phosphofructokinase 1
| produce: phosphoglycerate kinase, pyruvate kinase
102
fasting and fed state regulation of glucose handling by F2,6BP
fasting: inc glucagon > inc cAMP > inc PKA > inc FBPase2, dec PFK2, dec glycolysis
fed: inc insulin > dec cAMP > dec PKA > dec FBPase2, inc PFK2, more glycolysis
103
2 purely ketogenic AAs
lysine and leucine
104
pyruvate dehydrogenase complex deficiency - most common inheritance pattern, main sx, tx
x linked
neuro deficits
inc intake of ketogenic nutrients
105
4 different metab paths that pyruvate can take
to alanine via ALT
to oxaloacetate to replenish TCA cycle
to acetyl CoA to enter TCA cycle
to lactate to finish anaerobic glycolysis
106
which makes more ATP - 1 NADH or 1 FADH2?
NADH (3 vs 2)
107
rotenone, CN, antimycin A, and CO have what effect (all same) on metabolism?
electron transport inhibitors
108
ATP synthase inhibitor
oligomycin
109
why can't muscle do gluconeogenesis?
lacks glucose 6 phosphatase
110
3 products of HMP shunt
NADPH, ribose, glycolytic intermediates
111
where is the HMP shunt used?
lactating mammary glands, liver, adrenal cortex, RBCs
112
chronic granulomatous dz has a deficiency of what enzyme?
NADPH oxidase - needed to initiate respiratory burst
113
G6PD def pathophys
less G6PD > less NADPH > less protection from oxidation, esp in RBCs > hemolyitc anemia when exposed to oxidizing agents (fava beans, etc) or infections
114
G6PD def inheritanced
XLR
115
2 PBS findings in G6PD def
```
Heinz bodies (oxidized Hgb)
Bite cells (phagocytosed Heinz bodies in spleen leave "bite" in cell)
```
116
essential fructosuria
defect in fructokinase, AR, asymptomatic, fructose in blood and urine
117
fructose intolerance
def in aldolase B, AR
accum of fructose 1 phosphate > dec available PO4 > inhib glycogenolysis/gluconeogenesis
sx - hypoglycemia, jaundice, cirrhosis, vomiting
tx - dec intake of fructose and sucrose
118
galactokinase def
mild, AR
| galactose in blood/urine. infantile cataracts. may not track objects or develop social smile
119
classic galactosemia
no galactose-1-phosphate uridyltransferase > accum of toxic substances
failure to thrive, jaundice, hepatomegaly, infantile cataracts, mental retardation
tx - dont eat galactose/lactose
120
cells at risk for sorbitol accumulation
schwann cells, retina, kidney
121
essential AAs
Met Val His
Ile Phe Thre Trp
Leu Lys
122
Cori cycle
muscle uses glucose and makes lactate, shuttle to liver, where it is turned back into glucose and reenters bloodstream
123
hyperammonemia
can be congenital or acquired. excess NH4 > inhib TCA cycle
124
signs of ammonia intox
asterixis, slurring, somnolence, vomiting, cerebral edema, blurry vision
125
ornithine transcarbamoylase deficiency
MC urea cycle disorder - XLR
can't eliminate ammonia properly, buildup of orotic acid
inc orotic acid, dec BUN, hyperammonemia sx
126
catecholamine synth pathway
phenylalanine > tyrosine > dihydroxyphenylalanine (dopa) > dopamine > norepinephrine > epinephrine
127
dietary reqs of PKU
tyrosine becomes essential, strict phenylalanine restriction
128
sx of PKU
mental and growth retardation, seizures, fair skin, eczema, musty body odor
129
deficiency in PKU
phenylalanine hydroxylase or tetrahydrobiopterin cofactor
130
alkaptonuria
```
def in degradative pathway of tyrosine
AR, benign
dark connective tissue, brown sclera, urine turns black on prolonged exposure to air, debilatating arthralgias
```
131
3 causes of albinism
tyrosinase def
defective tyrosine transporters
lack of migration of neural crest cells
132
nutritition req in homocystinuria
cysteine becomes essential
133
3 forms of homocystinuria etiology
```
def cystathionine synthase
dec affinity of cystathionine synthase
homocysteine methyltransferase def
```
134
sx of homocystinuria
mental retardation, osteoporosis, tall stature, kyphosis, lens subluxation, atherosclerosis
135
cystinuria
defect in one of the AA transporters in PCT of kidney
> precipitation of hexagonal crystals and renal staghorn calculi
AR
tx w/ good hydration and urinary alkalinization`
136
maple syrup urine dz
AR
blocked degradation of branched AAs due to dec alpha ketoacid dehydrogenase > inc alpha ketoacids in blood
CNS defects, mental retardation, death
urine smells like maple syrup
137
hartnup dz
AR
defective neutral AA transporter in kidney and intestines
tryptophan excretion in urine and dec absorption in gut > pellagra
138
intracellular messenger that glucagon/epi increases
cAMP
139
4 glycogen storage diseases
Von Gierke's (type 1)
Pompe's (type 2)
Cori's (type 3)
McArdle's (type 4)
140
general sx of lysosomal storage disorders
peripheral neuropathy / demyelination, neurodegeneration, hepatosplenomegaly, cherry red spot in macula
141
Fabry's, Gaucher's, Niemann-Pick, Tay-Sachs, Krabbe's, Metachromatic leukodystrophy are examples of what kind of disorder?
lysosomal storage disease - sphingolipidoses
142
Hurler's and Hunter's diseases are what kind of disorders?
lysosomal storage disease - mucopolysaccharidoses
143
where does fatty acid degradation take place?
mitochondrion
144
carnitine deficiency
inability to transport LCFAs into mito > toxic accumulation
| weakness, hypotonia, hypoketotic hypoglycemia
145
which ketone is not detected by urine dipstick?
beta hydroxybutyrate
146
rate limiting step of cholesterol synth
HMG CoA reductase
147
```
which way do these lipid particles go (liver > periphery or vice versa)?
VLDL
IDL
LDL
HDL
```
VLDL - TGs to peripheral tissue
IDL - TGs and cholesterol to liver
LDL - cholesterol to tissues
HDL - cholesterol to liver
148
familial dyslipidemias - type 1 hyperchylomicronemia
AR
| pancreatitis, xanthomas, NO INC RISK FOR ATHEROSCLEROSIS
149
familial dyslipidemias - type 2a familial hypercholesterolemia
AD, absent or dec LDL receptor
| accelerated atherosclerosis
150
familial dyslipidemias - type 4 hypertriglyceridemia
AD, hepatic overproduction of VLDL
| pancreatitis
151
abetalipoproteinemia
AR
mutation in microsomal TG transfer protein (MTP) gene
dec chylomicron and VLDL synth > lipid accumulation in enterocytes
failure to thrive, steatorrhea, acanthocytosis, ataxia, night blindness
