Biochem Flashcards
(130 cards)
1
Q
tetrahydrobiopterin
A
used as cofactor in synthesis of tyrosine (phe–>tyr), dopamine (Tyr–>dopa), serotonin (tryptophan–>serotonin), and nitric acid
via dihydrobiopterin reductase
(def an uncommon cause of PKU)
2
Q
Cystic fibrosis
A
deletion of PHE at position 508 of CFTR gene
leading to defective protein-therefore less Cl transmembrane Cl channels
3
Q
MSH2 MLH1
A
Code for MUT L and Mut S
Mistmatch repair gene mutations
account for >90% Lynch (HNPCC) genetic defects
4
Q
sorbitol dehygrogenase
A
converts sorbital (made via glucose and aldose reductase) to fructose,
deficient in schwann cells, retinal and renal papilla leading to an accumulation in of sorbital
in lens the forward reaction has much less favorable kinetics and therefore can only keep up when small amounts of glucose are being converted to sorbitol
in states of hyperglycemia sorbital accumulates and cause deposits on lens and cataract formation
5
Q
AAs on T arm of tRNA
A
thymine, cytosine, pseudouracil
6
Q
sickle cell anemia gene defect
A
pt mutation in the 6th codon of the beta gene leading to valine (hydropobic) substitute for glutamic acid (hydrophilic)
-allowing for hydrophobic interactions and causing hb to aggregate in anaerobic conditions (more specifically bulging in beta chain fits in alpha chain hydrophobic region)
7
Q
aldolase B def
A
fructose intolerance
metabolizes fructose 1 p to DHAP and glycerol–prevents glycogenolysis and gluconeogenesis
avoid fructose and sucrose (glucose+fructose)
8
Q
mitochondrial metabolic pathways
A
beta oxidation of fatty acids, ketogenesis, TCA cycle, parts of urea cycle, pyruvate carboxylation
9
Q
AA deriv of NO
A
arginine
10
Q
AA deriv of urea
A
arginine and aspartate
11
Q
AA deriv of Heme
A
glycine and succinyl CoA
12
Q
AA deriv of creatinine
A
Glycine + arginine + SAM
13
Q
AA deriv of GABA
A
glutamate
14
Q
AA deriv of glutathione
A
Glutamate
15
Q
AA deriv of pyrimidines
A
Glutamate + Aspartate
16
Q
AA deriv of purines
A
Glutamate + Aspartate + Glycine
17
Q
AA deriv of histamine
A
histidine
18
Q
AA deriv of dopamine
A
Phe–>tyrosine–>Dopa–>dopamine
19
Q
AA deriv of melatonin
A
Tryptophan–>serotonin–>melatonin
20
Q
AA deriv of niacin
A
tryptophan
21
Q
AA deriv of Melanin
A
Tyrosine
22
Q
alpha galactosidase A def
A
Fabrys disease
accumulation of ceramide trihexoside
ancoparesthesias, angiokeratomas, heart/renal disease
23
Q
DNA methylation at CpG islands
A
represses transcription
24
Q
histone methylation
A
reversible represses DNA transcription
25
histone acetylation
relaxes DNA coiling and allows for transcription
26
GAG AAs
necessary for purine synthesis
Glutamine
Aspartate
Glycine
27
orotic acidura
```
defect in pyrimidine production
-hypochromic
megaloblastic anemia
growth retardation
excretion of high amounts of orotic acid in the urine
```
28
methotrexate/trimethoprime.pyrimethamine
all inhibit dihydrofolate reductase
29
adenosine deaminase deficiency
major cause of SCID
necessary for purine metabolism
leads to accumulation of adenosine which is toxic to lymphocytes
prevents DNA synthesis
30
Lesch Nyhan syndrome
defective absent HGPRT (hypoxanthine guanin phosphoribosyltransferase)
which converts gunaine to GMP and hypothanxine to IMP
excess uric acid production and de novo purine synthesis
-HGPRT
hyperuricemia
Gout
Pissed off (self mutilation, aggression)
Retardation
dysTonia
treatment: allopurinal or febuxostat (2nd line)
31
allopurinol/febuxostat
blocks conversion of hypoxanthine to xanthine and xanthine to uric acid
32
fluoroquinolones mech
inhibit topoisomerase II and IV
33
DNA pol III
5'-3' synthesis, 3'-5' exonuclease
34
DNA pol I
prok only
| same as DNA pol III but can excise RNA primer
35
sickle cell dz mutation
missense substitution of glutamic acid with valine
36
duchenne muscular dystrophy mutation
frameshift-resulting in truncated nonfuncitonal dystrophin protein
37
DNA repair of bulky helix distorting lesions
nucleotide excision repair
defective in xeroderma pigmentosa
-cannot fix thymine dimer induced by UV light
-increase aging, skin cancer (squamous cell carcinoma and malignant melanoma)
in G1 phase
38
DNA repair of single NT mistakes
Base excision repair
- glycosylase removes bad base creating an AP (apurinic/apyrimidic) site
- endonuclease cleaves 5' site
- lyase cleaves 3' site
- DNA pol fills in, ligase seals
39
mismatch nucleotides
```
-repair of newly synthesized strand
MUT S detects mismatch and recruits MUT L-exonucelase removes mismatch and DNA pol fills
-defective in HNPCC
in G2 phase
-
```
40
DNA repair of double stranded breaks
nonhomologous end joining
- 2 ends of DNA are brought together, may lose some DNA
- defective in ataxia telangiectasia and Fanconi anemia
- hypersensitive to ionizing radiation
41
ataxia telangiectasia
defective nonhomoloug DsDNA repair
-get cerebellar atrophy and repeated sino/pulmonary infections
-
42
amantia phalloides
mushroom cap
causes severe hepatotoxicity
-inhibits RNA pol II (makes mRNA)--[Pol I makes rRNA and III makes tRNA) -none have proofreading funciton
43
rifampin
inhibits RNA pol in prokaryotes
44
actinomycin D
inhibits RNA pol in euk and prok
45
p bodies
mRNA quality control, contain exonucleases, decapping enzymes and microRNAs -mRNA may be stored in P bodies and not used till much later
46
anti smith antibodies
highly specific for SLE
| antibodies against snRNPs (part of splicesome that take introns out of mRNA)
47
thymine pseudourasil cytosine
T arm of tRNA
| necessary sequence for binding with ribosome
48
D arm of tRNA
contains dihydrouracil necessary for tRNA recognition by correct amino-acyl tRNA synthetase
49
Li Fraumeni syndrome
have defect in p53, Rb tumor suppresors which normally regulate G1-->S phase progression
50
SER high in
liver, steroid hormone producing cells of adrenal cortex and gonads
51
mannose 6 phosphate signal
added by golgi-signals protein to lysosome
52
golgi modifications on proteins
modifies N-oligosaccharides on asparagine and adds O-oligosachhardises on serine and threonine
53
coarse facial features, clouded cornea, restricted joint movement,
- high lysosomal plasma levels
I cell disease
-defective N acetylglucosaminyl-1 phosphotransferase that leads to inability of golgi to add mannose signal to proteins
(usually fatal in childhood)
54
COPI
COPII
Clarthrin
COPI: retrograde--golgi trans--cis--ER
COPII: anterograde-ER--Cis--trans
Clathrin: endosomes -receptor mediated endocytosis-LDL receptor activity
55
dyenin
microtubule associated carrier protein
| works in retrograde fashion from + to - mt end
56
kinesin
microtubule associated carrier protein, works in anterograde fashion from - to + ends
57
```
int filaments staining
Vimentin
Desmin
cytokeratin
GFAP
Neurofilaments
```
```
vimentin-connective tissues
desmin-muscle
cytokeratin-epithelial tissues
GFAP-neuroglia
neurofilments-neurons
```
58
kartagener syndrome
primary ciliary dyskinesia
- immotile cilia due to dyenin arm defect
- infertile-no motile sperm and fallopian tube defect, bronchiectasis, recurrent sinusitis, situs inversus
59
digoxin/digitoxin
directly inhibit Na/K ATPase which indirectly inhibts Na/Ca exchange, making the cytoplasm have a high Ca content, increasing contractility
60
collagen type I
bone, skin, tendon, cornea
| -defective in OI
61
collagen type II
cartilage
62
collagen type III
reticulin-blood vessels, uterus, fetal tissues, granulation tissue
-defect rare-vascular type of Ehler Danlos syndrome
63
collagen type IV
basement membrane, lens, basal lamina
| -defective in alport syndrome, auto-antibodies directed against it in good pasture syndrome
64
best reflection of collagen synthesis
glycine-every 3rd residue
65
which step of collagen synthesis requires vitamin C?
hydroxylation of proline/lysine residues
66
menkes
defective collagen cross linking (lysine to hydroxy lysine) due to mt menkes protein leading to decreased copper absorption and therefore decreased activity of lysyl oxidase (needs copper)
-brittle, kinky hair, growth retardation, hypotonia
67
aging wrinkles
decreased collagen and elas tin FORMATION
68
FAVA beans
can precipitate hemolytic anemia in patients with glucose 6 dehydrogenase def. (used in HMP shunt) and therefore do not produce adequate NADPH necessary for RBS protection against ROS (used in reducing glutathione)
69
amyl nitrate
converts hemoglobin into methhemoglobin whic has low affinity for oxygen but high affinity for CN and shunts this away form organelles (mitochondria) where it would induce damage
70
pyruvate kinase deficiency
necessary for the conversion of phosphoenolpyruvate to pyruvate, producing ATP
-without it RBCs are hemolyzed bc of the insufficinect amount of ATP generated to maintain RBC cellular structure
71
measles supplementation
vitamin A
72
alkaptonuria
defective homogestisic acid oxidase-blocking tyrosine metabolism to fumarate, get accumulation of homogentistic acid which selectively accumulates in cartilage of ear, nose and turns black, also turns urine black
73
excessive egg white ingestion
leads to biotin deficiencey (avindin found in egg whites binds biotin making it inactive)
-biotin is necessary for the conversion of pyruvate to oxaloacetate in gluconeogeneiss)
74
burning feet syndrome
pantothenic acid deficiency (coenzyme A/vitamin B5)
-impt in the TCA cycle binds with oxaloacetate to form citrate
-also necessary for the production of Vitamin A, D, cholesterol, steroids, heme A, fatty acids, AAs, and proteins
causes feeet dysesthesias, paresthesias, edmea of lower extremities, chronic diarrhea, greasy stool
75
thiamine participates as a cofactor in which glucose metabolic pathways
1. part of pyruvate dehrogenase which converts pyruvate to acetyl coa
2. with alpha ketoglutarate dehydrogenase in the TCA cycle
3. HMP shunt with transketolase converting ribulose 5-p to G3P, F6P, and ribose5P
76
high intracellular NADH in the setting of hypoglycemia
indicative of alcohol ingestion-alcohol serves as a form of energy and through its metabolism creates NADH, high NADH then shunts pyruvate from TCA to lactate
77
cafe au lait spots, polyostotic fibrous dysplasia, percocious puberty, many endocrine abnormalities
McCune Albright Syndrome
- due to defect in G protein signaling, example of mosaicism,
- lethal if mutation occurs before fertilization
78
prader willi
imprinting of maternal gene. chromosome 15, paternal gene then deleted, results in hyperphagia, small gonads, obesity, intellectual disability, hypotonia
79
angelman
imprinting of paternal gene with subsequent maternal gene deleted/mutated, results in inappropriate laughter, seizures, ataxia, severe intellectual disability,
80
autosomal dominant diseases
```
ADPCKD-PKD1 gene chr 16
FAP-APC gene chr 5
Familial hypercholesterolemia
hereditary hemorrhagic telangiectasia
Hereditary shpherocytosis: defect in spectrin or ankyrn
Huntingtons disease CAG repeat chr 4
Li fraumeni syndrome: abnml Tp53 gene--many malignancies at a very young age
Marfan: defective fibrin gene FBN1 chr 13
MEN associated with RET gene
Myotonic dystrophy
NF1: NF1 ch 17
NF2: NF2 ch 22
tuberous sclerosis:
VHL: deletion of VHL chr 3
```
81
autosomal recessive diesases
CF, sickle cell anemia, ARpkd, glycogen storage disorderd, kartagener syndrome, mucopolysaccharidoses (except hunter), PKU, sphingolipidoses (except Fabrys) Thalassemia, Wilsons
82
X linked recessive diseases
```
Be Wise, Fool's GOLD Heeds SIlly Hope
Bruton agammaglobulinemia
Wiskott Aldrich syndrome,
Fabry,
G6PD,
Ocular albinism,
Lesh Nyhan,
Hunter SYndrome,
Hemophilia A and B,
Ornithine transcarbamylase A and B
```
83
myotonic dystrophy type 1
My tonia, my testicles, my toupee, my ticker
| CTG trinucleotide repeat of DMPK gene
84
fragile X syndrome
CGG nucleotide repeat of FMR1 gene
| -MR, macroorchidism, joint laxity, pes cavus, MVP, long face with large jaw
85
Trinucleotide expansion diseases
```
Huntinton (CAG)
myotonic dystrophy (CTG)
fragile X (CGG)
friedrich ataxia (GAA)
```
86
decreased PAPPA
increased b HCG
increased nuchal translucency
downs syndrome findings in first trimester
87
Decreased estriol
decreased alpha fetoprotein
increased b HCG
increased inhibin A
downs syndrome findigns in second trimester
88
rocker bottom feet, micrognathia, low seat ears, clenching hands,
Edwards syndrome trisomy 18, most die after 1 year
89
decreased PAPPA
| decreased b HCG
edwards syndrome (trisomy 18)
90
decrased alpha fetoprotein
decreased bHCG
decreased estriol
decreased PAPPA
edwards, trisomy 18
91
cleft lip/palate, holoprosencephaly, polydacytly, congenital heart disease, rocker bottom feet, micropthamnia
Patau trisomy 13
92
decreased b HCG
decreased PAPPA
increased fetal nuchal translucency
Patau syndrome trisomy 13
93
cardiac abnormalities, epicanthal folds, microcephaly, intellectual disability, mewing sound
cri du chat, congenital deletion of short arm of chromosome 5
94
elfin faces, intellectual disability, hypercalcemia (increased sensitivity to Vitamin D) well developed verbal skills, extreme friendliness to strangers, cardiovascular problems
williams syndrome
| congenital microdeletion of long arm of chromosome 7
95
CATCH22
```
microdeletion at chromosome 22q11
C: cleft palate
A: abnormal facies
T: thymic aplasia
C: cardiac defects
H: hypocalcemia 2/2 parathyroid aplasia
DiGeorge: thymic, parathyroid and cardiac defects
Velocardiofacial syndrome: palate, facial, and cardiac defects
```
96
dry scaly skin, night blindness, immunosuppresion, corneal degeneration, bitot spots on conjunctiva
Vitamin A deficiency
97
vitamin A excess
acute: N/V, blurred vision
Chronic: alopecia, dry skin, pseudotumor cerebri, arthralgias
teratogenic: cleft palate, cardiac abnormalities,
98
high output cardiac failure and LE edema
wet BerIBerI
| vitamine B1 def
99
polyneuritis, symmetrical muscle wasting
dry BerIBerI
| vitamin B1 def
100
increase in RBS transketolase activity following infusion of thiamine
diagnosis for B1 defiency (wenicke korsakoff/beriberi)
101
cheiliosis and corneal vascularization
vitamin B2 def
riboflavin
necessary for FAD.FMN
B2=2ATP
102
synthesis reactions requiring B6
- cystathione
- heme
- niacin
- histamine
- serotonin
- NE
- epi
- DOPA
- GABA
103
reactions which require Biotin
Vit B7
carboxylation reactions
-pyruvate carboxylase (pyruvate-->oxaloacetate)
-Propionyl carboxylase (propionyl CoA-->methylmalonyl CoA)
-AcetylCoA carboxylase (Acetyl Coa-->Malonyl CoA)
104
causes of B12 deficiency
colbalamin
(have pool stores for years in the liver)
-insufficient intake (veganism)
-malabsorption (celiac sprue, enteritis, Diphyllobothrium latum)
-lack of intrinsic factor (pernicious anemia, gastric bypass)
-absence of terminal ileum (Crohn disease)
105
function of Vitamin C (pathways)
hydroxylation of proline and lysine in collagen synthesis, dopamine Beta hydroxylase (converts dopamine to NE), facilitates absorption of iron by reducing to the Fe2+ ferric state
106
corskcre hair, easy bruising, sollen gums, petechiae, hemarthrosis, anemia, poor wound healing
SCURVY
107
ancillary treatment for methemoglobinemia
vitamin C
| -reduces Fe3+ to Fe2+
108
hemolytic anemia, acanthocytosis, posterior column and spinocerebellar tracy demyelination
Vitamin E deficiency
| -like B12 without megaloblastic anemia or hypersegmented neutrophils or increased serum MMA
109
dealyed wound healing, altered sense of tase/smell (dysgeusia/anosmia), acrodermatitis enteropathica
Zinc def
| -may predispose to alcoholic cirrhosis
110
Kwashiorkor
```
MEAL
malnutrition
edema
anemia
liver (fatty)
```
111
Marasmus
calorie malnutrition resulting in muscle wasting, edema loss of sub q fat
112
ATP production from glycolysis with arsenic poisoning
ZERO ATP
113
reactions involving Vitamin b6
transamination (an alpha keto acid joins with an AA to bceome an AA)
and in decarboxylation reactions
114
tender loving care for nancy
```
cofactors required by branched chain alpha dehydrgoenase, pruvate dehydrogenase and alpha keoglutarate dehydrognease
Thiamine
Lipoate
CoA
FAD
NAD
```
115
vomiting, rice water stools, garlic breath
arsenic poisoning-->inhibits lipoic acid (a key component of pyruvate dehydrogenase complex)
116
high orotic acid in blood, urine, decreased BUN, tremor, slurred speech, somnolence, vomiting, cerebral edema, blurred vision
high ammonia secondary to ornithine transcarbamylase deficiency
-difference between this and orotic aciduria is no megaloblastic anemia is seen here
117
hereditary dysfunction of PCT preventing absorption of COLA
```
cystinuria
-cystine
-ornithine
-lysine
-arginine
AT
urinary cyanide-nitroprusside test is diagnostic
-causes hexagonal stone to precipitate
tx: urinary alkalinization (potassium citrate, acetazolamide) and chletating agents (penicillamine)
```
118
intellectual disability, marfanoid, osteoporosis, lens subluxation, kyphosis, thrombosis, atherosclerosis
homocytinuria
- due to def in cystathionine synthase
treatment: decreased methionin, increase cysteine, increase b12/folate in diet
119
dark connective tissue, brown pigmented sclera, urine turns black on prolonged exposure to air
alkaptonuria
-due to def in homogentisate oxidase
can have debilitating arthralgias -homogentisic acid is toxic to cartilage
120
lactulose give with...
binds ammonia, acidifies GI tract
- given with rifaxamin to decrease colonic ammoniagenic bacteria
- benzoate or phenylbutyrate decrease ammonia by binding and causing its excretion
121
developmental delay, corneal clouding, gargoylism, airway obstruction
hunters
deficiency of alpha L iduronidase
get accumulation of heparan suflate dermatan sulfate
122
developmental delay, gargoylism, aggressive behavior, airway obstruction
hurlers
-iduronate sulfatase deficiency
get buildup of dermatan and hapran sulfate
123
central and peripheral ataxia with dementia, buildup of cerebroside sulfate
Metachromic leukodystrophy
| -def of arylsulfatase A
124
globoid cells, peripheral neruopathy,d evelopmental delya, optic atrophy
Krabbe disease
| buildup of galactocerebroside/psychosine due to def of galactocerebrosidase
125
cherry red spot, no HSM, progressive neurodegeneration, developmental delay, lysosomes with onion skin
```
tay sachs
def of hexosaminosidase A
```
126
cherry red spot, Hsm, developmental regression, fomay histocytes,
```
neiman picck
def of sphingomyelinase get accumulation of sphingomyelin
```
127
pancytopenia, HSM, asecptic necrosis of femur, bone crisis, osteoporosis, lipid laden macrophages that look like crinkled tissue paper
gauchers disease
| -def of glucocerebrosidase with accumulation of glucocerebroside
128
acroparesthesia, angiokeratomas, cardiovascular/renal
```
Fabrys
def of alpha galactosidase A with accumulation of ceramide trihexose
```
129
hypoketotic hypoglycemia with vomiting, lethargy, seizures, liver dysfunciton
```
def of medium chain acyl COA dehydrogenase
-disorder of fatty acid oxidation and therefore breakdown to acetyl coa
```
130
systemic primary carnitine def
cant transport long chain fatty acids into the mitochonria
| -toxic accumulation causing weakness, hypotonia and hypoketotic hypoglycemia
