lecture 11 Flashcards

1
Q

two biosynthesis pathways

A

De novo and Salvage

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2
Q

de novo synthesis

A

“new” synthesis

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3
Q

precursors for de novo

A

amino acids, ribose 5P, CO2, NH3

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4
Q

salvage pathway

A

endproducts made from “scavenged” components

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5
Q

how does the salvage pathway get precursors

A

Recycling of free bases and nucleosides from nucleic acid breakdown

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6
Q

what does de novo synthesis begin with

A

5-phosphoribosyl 1-pyrophosphate (PRPP)

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7
Q

what does de novo end with

A

inosinate (IMP)

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8
Q

biosynthesis of AMP and GMP:

A

IMP is an important precursor

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9
Q

arm 1 of IMP to AMP

A

add aspartate and GTP
take out fumerate
make adenylate

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10
Q

arm 2 of IMP to GMP

A

add H2O and reduce NAD
add amino group of glutamine and use ATP
make GMP

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11
Q

3 major inhibition mechanisms

A
  1. ribose phosphate pyrophosphokinase
  2. glutamine-PRPP amidotransferase
  3. AMP inhibiting adenylosuccinate synthetase
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12
Q

bacterial carbamoyl phosphate synthetase

A

3 active sites

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13
Q

substrate channeling

A

important in limiting substrate/intermediates diffusion

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14
Q

when is substrate channeling critical

A

if intermediates are unstable

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15
Q

aspartate transcarbamolyase

A

in charge of bacterial pyrimidine biosynthesis

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16
Q

ATCase

A

first enzyme in pyrimidine de novo synthesis pathway

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17
Q

what does ATP prevent

A

CTP-induced change in ATCase activity

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18
Q

CTP

A

causes extreme decline in ATCase activity

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19
Q

ribonucleotides

A

are precursors of deoxyribonucleotides

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20
Q

E coli ribonucleotide reductase

A

enzyme acts on ribonucleotide diphosphate

21
Q

what does the reduction involve

A

replacement of 2OH with H

22
Q

slide 12

A
23
Q

where does regulation of ribonucleotide reductase occur

A

at primary AND substrate specificity sites

24
Q

why does ribonucleotide reductase have 2 sites of regulation

A

idea is to provide a balanced pool of precursors for DNA synthesis

25
Q

both activity and substrate specificity are regulated by

A

effector building

26
Q

enzyme activity

A

ATP activates
dATP inactivates

27
Q

substrate specificity
when ATP or dATP is bound

A

favors reduction of UDP and CDP

28
Q

substrate specificity
when dTTP or dGTP is bound

A

favors reduction of GDP or ADP

29
Q

thymidine is derived from

A

dCDP and dUMP

30
Q

what does the degradation of purines and pyrimidines produce

A

uric acid and urea

31
Q

what exctretes allantoin

A

most mammals

32
Q

what excretes allantoate

A

bony fishes

33
Q

whats the difference between allantoin and allantoate

A

extra H2O

34
Q

catabolism of thymidine results in

A

methylmalonyl semialdehyde-> succinyl coa

35
Q

how are free purine and pyrimidine bases released

A

metabolic degradation of NTs

36
Q

adenine + PRPP

A

AMP +PPi

37
Q

where does the pyrimidine pathway exist

A

bacteria POSSIBLY mammals

38
Q

defect in which salvage pathway enzyme could cause Lesch- Nyhan syndrome

A

hypoxanthine-guanine phosphoribosyltransferase HGPRT

39
Q

lesch nyhan

A

almost exclusively male children
symptoms: mental retardation, self mutilation

40
Q

what do defects in HGPRT result in

A

elevated de novo purine synthesis & increases in uric acid

41
Q

gout

A

excess uric acid

42
Q

allopurinol

A

inhibitor of xanthine oxidase

43
Q

what is a strong inhibitor of xanthine oxidase

A

oxypurinol

44
Q

chemotherapeutics attack

A

nucleotide biosynthetic pathways

45
Q

two targets

A

thymidylate synthase, dihydrofolate reductase

46
Q

thymidilate synthase

A

FdUMP

47
Q

dihydrofolate reductase

A

methotrexate, aminopterin, trimethoprim

48
Q

suicide inhibitors (FdUMP)

A

reactive flourine binds to enzyme and makes dead end covalent complex