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Flashcards in Biochemistry-Molecular/Genetics Deck (76):
1

What is rate limiting step of de novo purine nucleotide synthesis?

glutamine PRPP (5-phosphoribosyl-1-pyrophosphate) amidotransferase; inhibited by downstream products: IMP, GMP, AMP; cofactors: THF, glutamine, glycine, aspartate

2

Lesch-Nyhan Syndrome

HGPRT (converts hypoxanthine to IMP and guanine to GMP); tx w/ allopurinol (inhibits xanthine oxidase); X linked recessive

3

Severe combined T and B immunodeficiency

Adenosine deaminase deficiency; causes excess ATP/dATP and inhibits ribonucleotide reductase creating imbalance in nucleotide pool; autosomal recessive

4

Hereditary orotic aciduria

orotate phosphoribosyl transferase and/or OMP decarboxylase deficiency

5

Amino acids required for purine synthesis

glycine, aspartate, glutamate (used by glutamine PRPP amidotransferase)

6

converts ribonucleotides to deoxyribonucleotides

ribonucleotide reductase (inhibited by dATP, feedback)

7

inhibits dihydroorotate dehydrogenase

leflunomide

8

inhibit IMP dehydrogenase

mycophenolate, ribavirin

9

inhibits ribonucleotide reductase

hydroxyurea

10

inhibits de novo purine synthesis

6-MP and azathioprine (6MP prodrug)

11

thymidylate synthase

5-FU

12

inhibits dihydrofolate reductase in humans, bacteria, or protozoa

methotrexate (humans), trimethoprim (bacteria), pyrimethamine (protozoa)

13

DNA polymerase III

5'-3' DNA synthesis; 3'-5' exonuclease activity

14

DNA polymerase I

5'-3' exonuclease activity, excises RNA primer (put down by primase)

15

endonuclease

nucleotide excision repair, base excision repair (glycosylase-AP site)

16

defective nucleotide excision repair

xeroderma pigmentosum--UV induced pryimidine dimers

17

defective mismatch repair

HNPCC

18

defective NHEJ

ataxia telengectasia

19

drugs that block DNA replication often have what modification?

3'-OH group to prevent addition of next nucleotide (DNA/RNA is synthesized 5'-3'

20

mRNA start codon

AUG (rarely GUG)

21

mRNA stop codons

UGA, UAA, UAG

22

inhibits RNA polymerase II

alpha-amantin (from death cap mushrooms); causes severe hepatotoxicity

23

cytoplasmic P bodies

mRNA quality control, contains exonucleases, decapping enzymes, microRNAs

24

anti smith antibodies

antibodies to spliceosomal snRNPs (highly specific for SLE)

25

anti U1 RNP

antibody to snRNP70--highly associated with mixed connective tissue disease

26

which end of tRNA carries amino acid? what sequence?

ALL tRNAs have a CCA on 3' end that carries AAs

27

T-ARM of tRNA

contains thymidine/pseudourine/cytosine sequence necessary for tRNA ribosomal binding

28

D-ARM of tRNA

contains dihydrouracil residues necessary for tRNA recognition by the correct aminoacle-tRNA synthetase

29

Anticodon loop of tRNA

binds mRNA and is opposite the ACC/amino acid end

30

charging tRNA

aminoacyl-tRNA synthetase, requires ATP, 1 per amino acid matchmaker; requires D-arm of ATP for correct binding

31

tRNA translocation/activation

requires GTP/ATP respectively

32

course facial features, clouded corneas, restricted joint movement, high plasma levels of lysosomal enzymes

I-cell disease: inherited lysosomal storage disorder, defect in phosphotransferase, failure of golgi to phosphorylate mannose residues-->proteins delivered extracellularly instead of to lysosomes

33

What specifics does the Golgi modify?

modifies N-oligosaccharides on asparagine, adds O-oligosaccharides on serine/threonine, adds mannose-6-phosphate to proteins for lysosomal trafficking

34

traffics protein from ribosome to RER

signal recognition particle (SRP); ribonucleoprotein; when deficient-->proteins accumulate in cytosol

35

retrograde trafficking

COP1

36

anterograde trafficking

COP2

37

trans-golgi trafficking

clathrin

38

vimentin

connective tissue

39

desmin

muscle

40

cytokeratin

epithelial cells

41

GFAP

neuroglial cells

42

neurofilaments

neurons

43

Type 1 Collagen; disease?

Bone, skin, tendon, dentin, fascia, cornea, late wound repair; osteogenesis imperfecta type I

44

Type 2 collagen

cartilage (including hyaline); vitreous body, nucleus puplosus

45

Type 3 collagen, disease?

reticulin--skin, blood vessels, uterus, fetal tissue, granulation tissue--Ehler Danlos vascular type

46

Type 4 collagen; diseases?

basement membrane, basal lamina, lens; alport syndrome, goodpasture syndrome

47

which step of collagen synthesis is defective in osteogenesis imperfect?

Glycosylation step; formation of procollagen via hydrogen and disulfide bonds to form triple helix of procollagen

48

which step of collagen synthesis is defective in Ehler Danlos?

Cross linking step; Cu2+ containing lysyl oxidase; final step to make collagen fibrils

49

multiple fractures with minimal trauma occurring during birth process

Osteogenesis imperfecta--autosomal dominant with decreased production of otherwise normal type I collagen; blue sclerae, hearing loss, dental imperfections

50

brittle/kinky hair, growth retardation, low muscle tone as child

Menkes disease--impaired copper absorption and transport--decreased activity of lysyl oxidase; problems crosslinking

51

hyperphagia, obesity, intellectual disability, hypogonadism, hypotonia

Prader Willi syndrome; maternal imprinting (paternal gene is deleted); chromosome 15

52

inappropriate laughter, seizures, ataxia, severe intellectual disability

Angelman Syndrome; paternal imprinting (materal gene deleted); chromosome 15

53

Example of x-linked dominant disorder

hypophosphatemic rickets (increased phosphate wasting at PCT)

54

myopathy, lactic acidosis and CNS disease

mitochondrial myopathy; failure in oxidative phosphorylation; muscle biopsy shows ragged red fibers; mitochondrial inheritance

55

ADPKD

autsomal dominant; PKD1 (chromosome 16); PKD2 (chromosome 4)

56

FAP

autosomal dominant; APC (chromosome 5; polyp has 5 letters)

57

telangectasia, recurrent nosebleeds, skin discoloration, AVMs, gi bleeding, hematuria

Hereditary hemorrhagic telangectasia, autosomal dominant, aka Osler Weber Rendu syndrome

58

Huntington disease

AD; chromosome 4; CAG repeats

59

cystic medial necrosis of aorta; floppy mitral valve, lens subluxation typically upward and temporally

Marfan syndrome--fibrillin 1 defect (sheath for elastin)

60

MEN syndromes inheritance pattern

autosomal dominant

61

cafe au lait spots and cutaneous neurofibromas

NF1, AD, chromosome 17

62

bilateral acoustic schwannomas, juvenile cataacts, meningiomas, ependymomas

NF2, AD, chromosome 22

63

numerous benign hamartomas

tuberous sclerosis--AD, incomplete penetrance, variable expression

64

retinal, medullary, cerebellar angiomas, bilateral renal cell carcinoma

von hippel lindau disease; AD, chromosome 3

65

cystic fibrosis

CFTR gene on chromosome 7; AR

66

Some autosomal recessive diseases:

albinism, ARPKD, CF, glycogen storage diseases, hemochromatosis and Wilsons, Kartagener, mucopolysaccharidoses (except Hunter syndrome X linked R); PKU, sickle cell, sphingolipidoses (except Fabry XLR w/ incomplete penetrance), thalassemias

67

X-linked Recessive disorders

Be Wise Fools GOLD Heeds Silly HOpe: bruton, wiskott-aldrich, fabry, G6PD, ocular albinism, Lesch Nyhan, Duchenne (and becker), hemophilia A/B, Hunter syndrome, OTC deficiency

68

myotonia, muscle wasting, frontal balding, cataracts, testicular atrophy, arrhythmia

Myotonic type 1 dystrophy--CTG repeats in CMPK gene

69

post-pubertal macroorchidism, long face with large jaw, large everted ears, autism, mitral valve prolapse

Fragile X syndrome--X-linked CGG repeats in FMR1 gene

70

What are the trinucleotide repeats in common repeat disorders:

X-Girlfriends First Aid Helped Ace My Test: Fragile X--CGG; Friedrich's ataxia--GAA; Huntington--CAG; Myotonic dystrophy--CTG

71

Imaging and lab findings in Down Syndrome

First trimester US: increased nuchal translucency, hypoplastic nasal bone; serum PAPP-A is decreased, free bHCG is elevated; Quad screen: decreased AFP and estriol; increased bHCG and inhibinA

72

Lab findings in Edwards syndrome

everything is down

73

US and Lab findings in Patau syndrome

everything is down, but increased nuchal translucency

74

microcephaly, moderate to severe intellectual disability, crying/mewing, epicanthal folds, cardiac abnormalities (VSD)

Cri du chat--microdeletion of short arm of chromosome 5 46XX/XY, 5p-)

75

elfin facies, intellectual disability, hypercalcemia, conversant, extremely friendly, cardiovascular problems

Williams Syndrome--microdeletion of long arm of chromosome 7

76

22qll deletion

Cleft palate, abnormal facies, thymic aplasia, cardiac defects, hypocalcemia (parathyroid aplasia)--defects in 3/4th branchial pouch formation--DiGeorge, velocardiofacial syndrome