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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
Q

6-mercaptopurine/ prodrug azathioprine

A

anticancer
inhibits PRPP–> IMP

*purine

26
Q

Mycophenolate

A

immunosuppressive

¬ Inhibit IMP dehydrogenase
¬ Inhibits IMP GMP
¬ Reduces proliferation of T and B cells
¬ Prevents organ transplant rejection

*purine

27
Q

Sulfonamides

A

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
Q

Allopurinol

A

Inhibits Xanthine Oxidase

¬ Increase in hypoxanthine and xanthine = more soluble than uric acid

29
Q

Azidothymide (AZD)

A

anti HIV

inhibits DNA polymerase

30
Q

acyclovir

A

anti herpes simplex virus

targets viral DNA polymerase & reverse transcriptase

31
Q

Acivicin

A

mostly GMP, anti Cancer

Gln Analog; inhibits nucleotide synthesis

32
Q

leflunomide

A

¬ Inhibits dihydroorate dehydrogenase

¬ Inhibits carbamoyl phosphate orotic acid

33
Q

hydroxyurea

A

inhibits ribonucleoside reductase

34
Q

5-FU

A

¬ Inhibits thymidylate synthase

¬ Inhibits dUMP dTMP

35
Q

Methotrexate

A

¬ 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
Q

RR activators and inhibitors

A

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
Q

CPS II: role, activators and inhibitors

A

CPS II: regulated step pyrimidines

Activated: PRPP, ATP
Inhibited: UTP, CTP

38
Q

PRPP Synthase Activators and inhibitors

A

Activators: Pi
Inhibitor: IMP, AMP, GMP

39
Q

End products Purine and pyrimidine synthesis

A

Purine:
ATP; dATP
GTP; dGTP

Pyrimidine:
UTP; dTTP
CTP; dCTP

40
Q

In what disorder is PRPP activity increased?

A

Lesch-Nyhan: HGPRT Defective

can’t convert
hypoxanthine–> IMP
guanine –> GMP

-IMP and GMP normally inhibit PRPP

41
Q

In what disorder is PRPP elevated?

A

Lesch-Nyhan: HGPRT Defective

can’t convert
hypoxanthine–> IMP
guanine –> GMP

-IMP and GMP normally inhibit PRPP

42
Q

What drug might inhibit the urine detection of OTC disorder? *my personal theory, not tested

A

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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