Biochemistry Flashcards
(146 cards)
1
Q
function - single-stranded DNA binding protein
A
stabilisation of unzipped DNA template strands
2
Q
genetic term ‘transversion’
A
point mutation resulting in purine being replaced with pyramidine or pyramidine replaced with purine c/o transition
3
Q
vitamin B9 name, deficiency (2)
A
folate/folic acid megaloblastic anaemia neural tube defect (foetus)
4
Q
carbomyl phosphate synthetase I deficiency
build up
blood findings
inheritance
A
- build up = NH4+
- blood findings = hyperammonaemia, low orotic acid, low BUN
- inheritance = AR
5
Q
Tay-Sachs disease
enzyme, buildup, features
A
- enzyme = hexosaminidase A deficiency
- build up - GM2 gangliosides
- clinical features = progressive neurodegeneration, developmental delay, ‘cherry-red spot’, lysosomes with onion skin, nil hepatosplenomegaly (c/o Niemann-Pick)
6
Q
vitamin B6 name, deficiency
A
pyridoxine cheilosis, stomatitis, glossitis
7
Q
homocystinuria enzyme, build up, features, Rx, inheritance
A
- enzyme = cysathionine beta-synthase
- build up = homocystine
- features = marfanoid body habitus, ectopia lentis, SpLD, thromboembolic occlusion
- Rx = methionine restriction, vitamin B6 (pyridoxine) supplementation
- inheritance = AR
8
Q
acute intermittent porphyria - treatment
A
haemin & glucose - ALA synthetase inhibitor
9
Q
Niemann-Pick disease enzyme, build up, features, histo
A
- enzyme = sphingomyelinase
- build up = sphingomyelin
- features = progressive neurodegeneration, hepatosplenomegaly, ‘cherry red spot’
- histo = foam cells (lipid laden macrophages)
10
Q
tetrahydrobiopterin reductase deficiency lab findings
A
elevated phenylalanine reduced serotonin and catecholamines elevated tryptophan
11
Q
function of glucose 6-phosphate dehydrogenase
A
convert glucose 6-phosphate to 6-phosphogluconate and NADP+ to NADPH
12
Q
McArdle disease type, enzyme, build up, features
A
Type IV glycogen storage disease
enzyme = glycogen phosphorylase (specifically, myophosphorylase)
build up = normal glycogen in muscles
features = exercise intolerance relieved by taking oral simple sugars, myoglobinuria
13
Q
Fructose intolerance enzyme, build up
A
- enzyme = aldolase B
- bulid up = fructose-1-phosphate
14
Q
blotting technique: northern
what does it detect and what is the reagent?
A
- detects = RNA
- uses = single stranded DNA or RNA
15
Q
tRNA struture: D loop
A
16
Q
Gaucher disease enzyme, build up, features, histo, Rx
A
- MOST COMMON
- enzyme = glucocerebrosidase
- build up = glucocerebroside
- findings = hepatosplenomegaly, pancytopenia, osteoporosis, aseptic necrosis of femur, bone crises
- Histo = gucher cells (lipid laden macrophages)
- Rx = recombinant glucocerebrosidase
17
Q
acute intermittent porphyria - deficiency in?
A
PBG deaminase deficiency
n.b. not enough to precipitate attack - must have inducer of ALA synthetase
18
Q
initiation of glycogenolysis; enzyme, its function and its control
A
- enzyme = glycogen phosphorylase
- function = removes glucose-1-phosphate from glycogen
- control = + glycogen phosphorylase kinase, - protein phosphatase
19
Q
urea cycle - intermediaries from citruline to ornithine, and the enzymes that form them
A
arginosuccinate synthase forms arginosuccinate
arginosuccinate lyase forms arginine
arginase forms ornithine
20
Q
vitamin B1 name, deficiency (2)
A
thiamine
Beriberi (peripheral neuropathy, heart failure) Wernicke-Korsakoff syndrome
21
Q
hyperchylomicronaemia (I)
A
increased = chylomicrons
deficiency = lipoprotein lipase or ApoC2
features = pancreatitis, hepatosplenomegaly, xanthoma
22
Q
Rx Zellweger syndrome
A
avoidance of chlorophyll
23
Q
vitamin C name, function
A
ascorbic acid
collagen proline and lysine residue hydroxylation
24
Q
genetic term ‘transition’
A
point mutation resulting in purine being replaced with purine or pyramidine replaced with pyramidine c/o transversion
25
Function - aconitase
catalyzes the isomerisation of citrate to isocitrate in the citric acid cycle
26
protein sequence change in HbS
glutamate (negative) to valine (nonpolar)
27
which tissue is GLUT-4 found?
adipocytes and skeletal muscle
28
What biochemical process is **Enolase** involved in?
something in glycolysis
29
tRNA structure: 3' end
CCA tail added as post-translational modification aka acceptor stem, for accepting the correct amino acid from aminoacyl-tRNA synthetase
30
medication that incurs oxidative stress on erythrocytes
6 total
* primaquine
* sulfa-containing drugs - co-trimoxasole - trimethoprim - sulfasalazine - sulfadiazine - sulfamethoxazole
31
in which cell type can glycolysis yield no ATP and why?
erythrocytes the production of 2,3-bisphosphoglycerate shunts glycolysis intermediates before net positive ATP yield is achieved, in order to increase oxygen delivery to end organs in lower blood oxygen levels
32
Effects of alcohol on the liver (HALF)
* H - hypoglycaemia
* A - Acidosis (lactic)
* (L - in the liver)
* F - fatty change (steatosis)
33
porphyria with neuropsychiatric symptoms likely due to which enzyme deficiency? disease name?
will be early step enzyme --\> PBG deaminase acute intermittent porphyria
34
lab findings - methylmalonic acidaemia
(AR mutation in methylmalonyl CoA mutase) acidaemia ketosis increased urine propionic acid hypoglycaemia hyperammonaemia
35
vitamin B9 name, function
folate/folic acid methyl group carrier - purine and thymine synthesis
36
metabolism 1 g of alcohol = ? cal
7
37
process of base excision repair
**base-specific glycosylase** - endonuclease - lyase - DNA polymerase - DNA ligase
38
Lesch-Nyhan syndrome enzyme, build up, features, Rx
* enzyme = HGPRT (hypoxanthine-guanine phosphoribosyltransferase)
* build up = uric acid
* features = high serum urate, gout, aggression/irritability, SpLD, dystonia
* Rx = allopurinol, febuxostat (xanthine oxidase inhibitors)
39
role of vitamin C/ascorbic acid
cofactor for hydroxylation of proline and leucine residues on procollagen fibers
40
familial hypercholesterolaemia (IIa)
* increased = LDL, cholesterol
* deficiency = LDL receptors
* features = atherosclerosis, xanthoma, corneal arcus
41
Essential fructosuria enzyme, build up, features
* enzyme = fructokinase
* build up = fructose
* features = none
42
hypertrigliceridaemia (IV)
* increased = VLDL, TGs
* patho = POLYGENIC increased VLDL production in liver
* features = acute pancreatitis
43
Kartagner's syndrome define, clinical features
* B/g = genetic defect in dynein protein, ciliary dysfunction
* clin features = sinusitis, otitis media, pneumonia, bronchitis, male infertility
44
vitamin B6 name, function
pyridoxine
transaminase cofactor
45
VLCFA and branched chain fatty acids broken down where?
peroxisome
46
hepatic amino group acceptor for transamination
alpha-ketoglutarate (Always)
AA + alpha-ketoglutarate --\> TCA intermediary + glutamate
47
mRNA stop codons
UGA (U go away) UAA (U are away) UAG (U are gone)
48
phenylketonuria (PKU) define, features, Rx
* b/g = **phenylalanine hydroxylase** deficiency, build up of PhenylAla, deficiency of tyrosine
* features = mental retardation, **albinism**, growth restriction, **musty odour**
* Rx = aspartame/phenylalanine restricted diet, tyrosine supplement
49
von Gierke disease type, enzyme, build up, features
Type I enzyme = glucose 6-phosphatase
build up = glucose 6-phosphate
features = hepatomegaly and steatosis, fasting hypoglycaemia, lactic acidosis, hyperuricaemia and gout
50
vitamin B1 name, function
thiamine decarboxylation of alpha-keto acids (carbohydrate metabolism)
51
mRNA start codon
AUG
52
which tissue is GLUT-5 found?
fructose transporter in spermatocytes
53
lab findings - B7 deficiency
hyperammonaemia hypoglycaemia metabolic acidosis and ketosis normal urine methylmalonic acid
54
Marfan's syndrome define, features,
* b/g = fibrillin gene mutation, fibrillin component of extracellular matrix
* features = arachnodactyle, hypermobility, high arching palate, AAA, valvular disease, retinal detachment, lens dislocation, aortic dissection, pectus excavatum
55
I-cell disease define, features, lab findings
* B/g = golgi cannot phosphorylate mannose residues on lysosomal enzymes so are trafficked out to cell membrane
* features = coarse facial features, clouded cornea, restricted joint movement
* findings = lysosomal enzymes in serum
56
key enzyme in de novo purine synthesis
PRPP phosphoribosyl pyrophosphate
57
role of PNMT control highest concentration in body?
conversion of norAd to adrenaline under control of cortisol highest concentration in adrenal medulla
58
sugars detected by copper reduction test
Reducing sugars: fructose glucose galactose
59
which tissue is GLUT-3 found?
placenta and neurons
60
Fabry disease enzyme, build up, features
* enzyme = alpha-galactosidase A
* build up = ceramide trihexoside
* findings = peripheral neuropathy, angiokeratoma, cardiovasular/renal disease
61
vitamin B12 name, function
cobalamin isomerase and methyltransferase cofactor (DNA and methionine synthesis)
62
DNA Pol III
5' to 3' DNA synthesis 3' to 5' exonuclease "proofreading" activity
63
Function - primase (RNA polymerase)
synthesis of RNA primer
64
DNA ligase
joining of okazaki fragments
65
blotting technique = southwestern
detects = DNA-binding proteins
uses = double-stranded DNA
66
tRNA structure: T loop
contains TpsiC motif
* T = ribothymidine
* psi = pseudouridine
* C = cystidine
Factilitates binding to ribosome
67
exclusively ketogenic amino acids
lysine leucine isoleucine tryotophan tyrosone phenylalanine
68
Function - helicase
unwinding of double helix
69
biotin (vitamin B7) deficiency association, enzymes affected, clinical features
* egg white consumption (biotin-binding avadin)
* enzymes = pyruvate carboxylase, acetyl-CoA carboxylase, propionyl-CoA carboxylase
* features = macular dermatitis, metabolic acidosis (pyruvate to lactic acid shunt, propionyl CoA to methylmalonyl CoA)
70
process of nucleotide excision repair
endonuclease - DNA polymerase - DNA ligase
xeroderma pigmentosum
71
cholesterol 7-alpha reductase function, implication in pathology, pharmacologic inhibition
* function = rate limiting step in bile salt formation from circulating cholesterol.
* pathology = malfunction results in decreased bile salt:cholesterol ratio predisposing to gall stone formation
* inhibition = fibrate drugs (fenofibrate, gemifibrozil)
72
Cori disease(s) type, enzyme, build up, features
Type III enzymes = debranching enzymes (alpha 1,6-glucosidase)
build up = very short branching chain glycogen
features = hepatomegaly, ketotic hypoglycaemia, weakness - LACTATE normal
73
Substrates needed for NAD+ production
Niacin (B3), nicotinamide
Tryptophan can endogenously make niacin
74
porphyria with photosensitivity likely due to which enzyme deficiency? disease name?
will be late step enzyme --\> UroD (uroporphyrinogen decarboxylase) porphyria cutanea tarda (PCT)
75
vitaminB2 name, function
riboflavin mitochondrial electron carrier
76
metabolism 1 g of fat = ? cal
9
77
familial dysbetalipoproteinaemia (III)
increased = chylomicrons and VLDL (decreased HDLs)
deficiency = ApoE
features = xanthoma, xanthoma striatum palmare, atherosclerosis
78
role of COMT
breakdown of catecholamines adrenaline --\> metanephrine norAd --\> normetanephrine
79
alkaptonuria enzyme, bulid up, features
enzyme = homogentisic acid dehydrogenase
build up = homogentisate - intermediate break down product of tyrosine when it doesn't go on to make DOPA (melanin and catecholamines)
features = arthritis, ankylosis, blue-black sclera and ears
80
metabolism 1 g of protein = ? cal
4
81
role of vitamin B12 (cobalamin)
cofactor for methylmalonyl CoA mutase converts methylmalonyl CoA to succinyl CoA which enters the TCA cycle for gluconeogenesis
82
clinical findings: hyperammonaemia
cerebral oedema, vomiting, hyperventilation, lethargy, blurred vision
83
Methanol poisoning toxins, biochemical pathway, features, Rx
* toxins = antifreeze, paint thinner, moonshine
* b/g = formaldehyde is toxic clearance product
* features = snow storm vision, death
* treatment = fomepezole and alcohol (competitive inhibition)
84
initiation of glycogenesis
enzyme = glycogen synthase
function = bind UDP-glucose together into glycogen
control = + insulin receptor and protein phosphatase, - PKA
85
vitamin B1; name, 4 enzymes dependent on it
thiamine
1. pyruvate dehyrogenase
2. alpha-ketoglutarate dehydrogenase
3. branched chain a-keto acid dehydrogenase
4. transketolase (ribulose 5-P to glyceraldehyde 3-P)
86
Essential amino acids
PVT TIM HALL P - phenylalanine, V - valine, T - threonine, T - tryptophan, I - isoleucine, M - methionine, H - histidine, A - Arginine - L - Leucine, L - lysine
87
primary carnitine deficiency enzyme, build up, clinical features (3)
* plasma membrane carnitine transporter
* fatty acids in cytoplasm - cannot enter mitochondria for beta-oxidation or ketone body production
* myopathy, cardiomyopathy, hypoketotic hypoglycaemia (eventually encephalopathy)
88
metabolism 1 g of carbohydrate = ? cal
4
89
Pompe disease type, enzyme, build up, features
* Type II
* enzyme = acid alpha 1,4-glucosidase/acid maltase
* build up = lysosomes containing glycogen
* features = normal glucose levels in the blood, severe CARDIOMEGALY, exercise intolerance, hepatomegaly, infant death
90
blotting technique = southern
detects = DNA
uses = single stranded DNA or RNA
91
which is the insulin dependent GLUT?
GLUT-4
92
vitamin B12 name, deficiency
cobalamin
megaloblastic anaemia, peripheral neuropathy (subacute combinded degeneration of the spine)
93
urea cycle - rate limiting step, enzyme, regulator and subcellular location
* step = CO2 + NH4+ + ATP --\> carbomyl phosphate
* enzyme = carbomyl phosphate synthetase I
* regulator = n-acteylcystine (positive, only available in excess aa)
* location = mitochondrial matrix
94
blood results in urea cycle dysfunction
hyperammonaemia increased glutamine in blood decreased blood urea nitrogen
95
poison mushrooms contain? what does this inhibit? clinical features?
* amatoxin
* RNA Pol II
* abdo pain, NandV, watery diarrhoea with blood and mucus. acute hepatic and renal failure, death.
96
amino acids required for purine synthesis
GAG G - glycine A - aspartate G - glutamine
97
which tissue is GLUT-1 found?
erythrocytes and BBB
98
Haemoglobin C mutation
glutamate (negative) to lysine (positive)
99
Function - topoisomerase II
removal of supercoils
100
Growth hormone receptor type and main function
type = JAK-STAT activator, NOT a RTK.
function = increase transcription of IGF-1
101
ornithine transcarbomylase (OTC) deficiency build up blood findings inheritance
* build up = carbomyl phosphate, shunting to pyrimidine pathway which produced orotic acid blood
* findings = hyperammonaemia, HIGH orotic acid, low BUN
* inheritance = XR
102
adenosine deaminase deficiency enzyme, build up, features
enzyme = adenosine deaminase
build up = ATP and deoxyATP, inhibition of ribonucleotide reductase, decreased DNA synthesis, decreased lymphocyte count
features = SCID
103
which tissue is GLUT-2 found?
liver, renal tubule (basolateral), islet beta cells, small intestine mucosa
104
DNA Pol I (3)
* 5' to 3' DNA synthesis
* 3' to 5' exonuclease "proofreading" activity
* Removal of RNA primer, replaces it with DNA
105
role of MAO
breakdown of catecholamines metanephrine and normetanephrine to vanillylmandelic acid
106
Renal ammoniagenesis
Glutamine - glutamate - a-ketoglutarate - glucose
products = NH3+ and HCO3- mechanism of increased acid excretion in chronic acidosis
107
vitamin B3 name, function
niacin electron transfer reactions (NAD, NADP)
108
vitamin B3 name, deficiency
niacin
pellagra - dermatitis, dementia, diarrhoea
109
2 functions of NADPH
cholesterol and fatty acid synthesis glutathione antioxidant mechanism
110
vitamin B2 name, deficiency symptoms
riboflavin
angular stomatitis, glossitis normocytic anaemia
111
Osteogenesis Imperfecta define, features
# define = collagen type I deficiency
features = blue sclera, joint pain, recurrent #, hearing loss. parent accused of child abuse
112
blotting technique = western
detects = protein
uses = antibodies
113
tetrahydrobiopterin (BH4) is required for synthesis of? (3)
1. tyrosine from phenylalanine
2. DOPA from tyrosine (catecholamines and melanin)
3. seretonin from tryptohpan
114
clinically - arthritis and ankylosing spondylitis
what disease? What builds up? enzyme deficiency? special lab finding?
Alkaptonuria
Homogentisic acid
homogentisic acid dioxygenase
Urine turns purple/black when left in air as homogentisate is oxidised
115
gross cerebral pathology - periaqueductal grey matter and mammillary bodies haemorrhage and necrosis
disease? epidemiology? deficit? enzyme affected?
Wernicke's encephalopathy
Alcoholics
B1 - thiamine
transketolase (PPP), pyruvate dehydrogenase, alpha-ketoglutarate dehyrogenase, branched chain alpha-keto acid dehydrogenase (catabolism of branched chain amino acids)
116
pellagra-like skin erruptions, cerebellar ataxia, neutral amino acids detected in the urine...
disease? deficiency? treatment?
Hartnup disease - neutral amino acid transporter impairment. of note is deficiency in tryptophan that makes up to 50% of NAD+ in the body.
NAD+ deficiency
high protein diet, niacin and nicotinamide replacement.
117
2 causes of elevated orotic acid?
1. uridine monophosphate (UMP) synthase deficiency (megaloblastic anaemia with no ammonaemia)
2. OTC deficiency (with ammonaemia)
118
in what situation does glycolysis of one glucose molecule yeild 1 molecule of pyruvate, but no net ATP?
in erythrocytes when 1,3-bisphosphoglycerate is shunted to produce **2,3-BPG** during **hypoxia** to decrease Hb oxygen affinity, and deliver more oxygen to target tissues
enzyme = **bisphosphoglycerate mutase**
119
what is the DNA damage caused by UV-B?
pyrimidine dimers, then causes double stranded break when it comes to replication
120
genetic principle
NF1 patients with different disease severity
variable expressivity
121
genetic principle
not all *BRCA1* gene mutations results in breast cancer
incomplete penetrance
122
genetic principle
single gene disorder PKU manifests in light hair, musty body odour and intellectual disability
pleiotropy
123
genetic principle
trinucleotitde repeat diseases become more severe in progressive generations
anticipation
124
genetic principle
heterozygous autosomal recessive inheritance with environmental damage to the wild type allele results in disease
common examples?
Two-hit hypothesis, loss of heterozygosity
HNPCC, Li fraumeni (p53), retinoblastoma
125
genetic principle
mutation to one allele of a transcription factor in its allosteric site, allowing binding to promoter sequence but no activation
dominant negative mutation
126
explain the importance of germline mosaicism
germline (gonadal) mosaicism = gene mutation occurs in the sperm or egg
offspring genotypically distinct from family.
incidence of genetic disorder in previously unaffected family
127
2 mechanisms by which ionizing radiation causes cell death
1. DNA double-strand breakage
2. free radical formation
128
what are the 5 diseases caused by meiotic nondisjunction?
trisomy 13, 18, 21
turner syndrome (45, X)
Klinefelter (47 XXY)
129
*VHL* is found at which locus?
ch 3p
130
which are the purines?
A and G
131
what are the pyrimidines?
C, T & U
132
what part of the cell cycle is a primary oocyte held in?
prophase of meiosis I
133
before fertilisation, the seconday oocyte is frozen in what phase of the DNA cycle?
metaphase of meiosis II
134
genetic inheritance of PKU?
autosomal recessive
135
mutation in transthyretin causes what diseases?
transthyretin = prealbumin
mutation leads to misfolding and tissue deposition; familial amyloid polyneuropathy & familial amyloid cardiomyopathy
136
which histone subprotein binds the nucleosome/DNA core from the outside, rather than form part of the middle?
H1
others (H2A, H2B, H3, H4) all form the nucleosome core around which the DNA is coiled
137
what is the Kozak consensus sequence and what is its function?
(gcc)gccRccAUGg
initiation of **translation**, so this refers to mRNA sequence
R = purine, A or G; AUG = methionine start codon
138
what enzyme produces mRNA in the eukaryotic nucleus?
nuclear RNA Polymerase II
139
explain enhancer sequences
enhancer - located upstream, downstream or within a gene. can be very far away.
can promote or enhance transcription
bind activator or silencer proteins, which alter RNA Pol II and TFs binding to promotor region of genes
140
pathoG - blotchy red muscle fibres on Gomori trichrome stain
mitochondrial myopathy (MERRF, Leber optic neuropathy, MELAS)
141
what are the numbers relevant to CGG trinucleotide repeats in fragile X syndrome?
5 - 55 is normal
\> 200 is complete mutation = fragile X syndrome
CGG TNRs results in *FMR1* hypermethylation and reduced expression, thereby impairing proper neurological development
142
what do alopecia, epilepsy and glaucoma have in common?
polygenic inheritance
143
Homeobox genes are mainly responsible for coordination of which body axis?
cranio-caudal
144
what is the most common mutation in cystic fibrosis and what is the effect?
deletion of phenylalanine (delF508)
impaired post-translational processing - resulting protein targeted to proteasome and unable to reach cell surface
145
what are the 3 inheritance patterns for down syndrome?
mitotic nondisjunction 95%
unstable Robertsonian transloc ation 2-3%
early embryonic nondisjunction (mosaicism) \<2%
146
inheritance of neurofibromatosis types 1 and 2
NF1 - autosomal dominant Ch 17 with highly variable presentation, *NF1* gene
NF2 - autosomal dominant microdeletion syndrome Ch 22q12 "*Merlin*" gene
