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Dems Unit 2 Part 2 YAAAY > Purine and Pyrimidine Metabolism > Flashcards

Purine and Pyrimidine Metabolism Flashcards

1
Q

purine source of atoms

A

aspartate, glycine, glutamate

*also needs THF for synthesis

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2
Q

pyrimidine source of atoms

A

aspartate

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3
Q

Purine de novo synthesis important enzymes

A

GLutamine Phosphoribosyl Pyrophosphate Amidotransferase

PRPP synthase: activated by Pi, Inhibited by IMP, GMP, AMP

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4
Q

Pyrimidine de-novo synthesis important enzymes

A

carbamoyl phosphate synthase II (cytosol): activated by PRPP, Inhibited by UTP

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5
Q

Purine Breakdown Products

A

uric acid = closed base ring

excreted in urine

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6
Q

pyrimidine breakdown products

A

open base ring

water soluble products used in other reactions

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7
Q

Purine synthesis steps

A
  1. glutamine phosphoribosyl pyrophosphate aminotransferase

PRPP + Glutamine –> PRPP + first nitrogen

  1. PRPP synthase
    Ribose 5 phosphate –> PRPP
    *involves several AA, CO2, THF, and ATP

Bases Produced:
IMP–> GMP
IMP–>AMP

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8
Q

failure of enzymes involved in AMP synthesis

A

associated with autism

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9
Q

feedback loop purine synthesis

A

IMP, GMP, AMP inhibit enzymes acting early in pathway

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10
Q

Pyrimidine synthesis steps

A
  1. carbamoyl phosphate synthase II
    PRPP + Glutamine –> PRPP + first nitrogen

Nucleotides:
First: UMP, to make cysteine nucleotides converted to triphosphate form
UMP–> UTP–> CTP

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11
Q

UMP synthase Deficiency

A

orotic aciduria

severe anemia, poor growth, orotate excreted in urine

Treat: feed synthetic uridine to supply pyrimidine nucleotides needed for DNA/RNA synthesis

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12
Q

Purine Breakdown steps

A
  1. remove free base from sugar –> free base (adenosine/guanine)
  2. free bases –> uric acid –> urine
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13
Q

pyrimidine breakdown steps

A
  1. remove base ring from ribose
  2. open base ring

Breakdown products: h20 soluble and used in other pathways (succinyl CoA, malonyl Co-A, acetyl Co-A)

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14
Q

important enzyme in purine breakdown

A

Xanthine Oxidase:

Hypoxanthine –> Xanthine –> Uric Acid

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15
Q

base specific nucleoside monophosphate kinases

A

Produces diphosphates: M–>D *bi-directional reactions

adenylate kinase
AMP + ATP –> 2ADP

Guanylate kinase
GMP + ATP –> GDP + ADP

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16
Q

nucleoside diphosphate kinase

A

produces triphosphates: D–>T

GDP + ATP –> GTP + ADP
CDP + ATP –> CTP + ADP

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17
Q

what enzyme converts ribose to deoxyribose?

A

ribonucleotide reductase

operates on diphosphate
Regulation based on Primary Regulation Site and Substrate specificity site

18
Q

regulation of conversion of ribose to deoxyribose

A

Ribonucleotide Reductase

Primary Regulation Site: On/ Off, Active= ATP, Inactive = dATP

Substrate specificity Site: Dial: sensitive to concentrations of dNTPs
–> makes sure that equal and adequate amounts of each NDP–> dNDP then to dNTPs

19
Q

ribonucleotide reductase reactions

A

GDP –> dGDP *Purine
ADP –> dADP *Purine
UDP –> dUDP *Pyrimidine

20
Q

how to make what is needed for DNA

A

dUDP dephosphorylated to make dUMP
Thymidylate synthase: dUMP –> dTMP
Kinases: dTMP–> dTDP –> dTTP

21
Q

SCID

A

Cause: mutated adenosine deaminase (of purine degradation pathway)

Description: imbalances pool nucleotide feedback inhibition of ribonucleotide reductase through dATP buildup; dNTPs are not made

Prevents DNA synthesis; lowers lymphocyte count

22
Q

Gout

A

cause: abnormal purine degredation pathway
description: uric acid builds up in blood; monosodium rate crystal deposit –> inflammation in joints

23
Q

Gout Treatment

A

Under Excrete: Increase excretion
Uricosuric drugs: probenecid or sulfinpyrazone

Over Producers:
allopurinol

Both Types:
anti-inflammatory: NSAIDS
Colchicine: stops polymerization of microtubules: inhibits neutrophil migration

24
Q

Lesch- Nyhan Syndrome

A

X linked recessive
Cause: deficient enzymes in purine salvage pathway (HGPRT): higher de novo rates of purine synthesis, excessive acid production

Description: HGPRT
Hyperuricemia
Gout
Pissed off (aggression, self-mutilation)
Retardation
T: DysTonia
25
6-mercaptopurine/ prodrug azathioprine
anticancer inhibits PRPP--> IMP *purine
26
Mycophenolate
immunosuppressive ¬ Inhibit IMP dehydrogenase ¬ Inhibits IMP GMP ¬ Reduces proliferation of T and B cells ¬ Prevents organ transplant rejection *purine
27
Sulfonamides
Inhibit bacterial purine synthesis ¬ Analogs of PABA ¬ Competitively inhibit folic acid synthesis by bacteria ¬ Inhibits synthesis of THF ¬ Slows purine synthesis pathway in microorganisms ¬ Humans do not synthesize folic acid: source= diet
28
Allopurinol
Inhibits Xanthine Oxidase ¬ Increase in hypoxanthine and xanthine = more soluble than uric acid
29
Azidothymide (AZD)
anti HIV | inhibits DNA polymerase
30
acyclovir
anti herpes simplex virus | targets viral DNA polymerase & reverse transcriptase
31
Acivicin
mostly GMP, anti Cancer Gln Analog; inhibits nucleotide synthesis
32
leflunomide
¬ Inhibits dihydroorate dehydrogenase | ¬ Inhibits carbamoyl phosphate orotic acid
33
hydroxyurea
inhibits ribonucleoside reductase
34
5-FU
¬ Inhibits thymidylate synthase | ¬ Inhibits dUMP dTMP
35
Methotrexate
¬ Inhibits dihydrofolate reductase ¬ Decreased dTMP ¬ Inhibits growth of cancer cells and bacterial growth ¬ Inhibits synthesis of THF and slows purine synthesis pathway Toxic for all dividing cells
36
RR activators and inhibitors
RR promotes the production of DNA nucleotides to balance RNA: - RNA nucleotides activate: ATP, GTP, UTP, CTP - DNA Nucleotides inhibit: dATP, dGTP, dTTP, dCTP
37
CPS II: role, activators and inhibitors
CPS II: regulated step pyrimidines Activated: PRPP, ATP Inhibited: UTP, CTP
38
PRPP Synthase Activators and inhibitors
Activators: Pi Inhibitor: IMP, AMP, GMP
39
End products Purine and pyrimidine synthesis
Purine: ATP; dATP GTP; dGTP Pyrimidine: UTP; dTTP CTP; dCTP
40
In what disorder is PRPP activity increased?
Lesch-Nyhan: HGPRT Defective can't convert hypoxanthine--> IMP guanine --> GMP -IMP and GMP normally inhibit PRPP
41
In what disorder is PRPP elevated?
Lesch-Nyhan: HGPRT Defective can't convert hypoxanthine--> IMP guanine --> GMP -IMP and GMP normally inhibit PRPP
42
What drug might inhibit the urine detection of OTC disorder? *my personal theory, not tested
Leflunamide: -excess carbamoyl phosphate from OTC becomes substrate in pyrimidine synthesis --> increased orotic acid production and urinary excretion Leflunamide inhibits carbamoyl phosphate -->orotic acid so could theoretically decrease urine production

Dems Unit 2 Part 2 YAAAY (23 decks)

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