lecture 11 Flashcards

(48 cards)

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

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
both activity and substrate specificity are regulated by
effector building
26
enzyme activity
ATP activates dATP inactivates
27
substrate specificity when ATP or dATP is bound
favors reduction of UDP and CDP
28
substrate specificity when dTTP or dGTP is bound
favors reduction of GDP or ADP
29
thymidine is derived from
dCDP and dUMP
30
what does the degradation of purines and pyrimidines produce
uric acid and urea
31
what exctretes allantoin
most mammals
32
what excretes allantoate
bony fishes
33
whats the difference between allantoin and allantoate
extra H2O
34
catabolism of thymidine results in
methylmalonyl semialdehyde-> succinyl coa
35
how are free purine and pyrimidine bases released
metabolic degradation of NTs
36
adenine + PRPP
AMP +PPi
37
where does the pyrimidine pathway exist
bacteria POSSIBLY mammals
38
defect in which salvage pathway enzyme could cause Lesch- Nyhan syndrome
hypoxanthine-guanine phosphoribosyltransferase HGPRT
39
lesch nyhan
almost exclusively male children symptoms: mental retardation, self mutilation
40
what do defects in HGPRT result in
elevated de novo purine synthesis & increases in uric acid
41
gout
excess uric acid
42
allopurinol
inhibitor of xanthine oxidase
43
what is a strong inhibitor of xanthine oxidase
oxypurinol
44
chemotherapeutics attack
nucleotide biosynthetic pathways
45
two targets
thymidylate synthase, dihydrofolate reductase
46
thymidilate synthase
FdUMP
47
dihydrofolate reductase
methotrexate, aminopterin, trimethoprim
48
suicide inhibitors (FdUMP)
reactive flourine binds to enzyme and makes dead end covalent complex