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DEMS Unit 3 > Purine and Pyrimidine Metabolism > Flashcards

Purine and Pyrimidine Metabolism Flashcards

1
Q

Nucleoside

A

base + pentose sugar

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2
Q

Nucleotide

A

Base + phosphorylated pentose sugar

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3
Q

Source of purines and pyrimidines in the body

A

de novo synthesis from other component molecules, or through recycling of pre-existing bases and combining with sugar moieties

diet –> minimal contribution

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4
Q

Activators and inhibitors of PRPP synthetase

A

Activator: Pi
Inhibitors: purine ribonucleotides

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5
Q

Key regulated steps in purine de novo synthesis

A

PRPP + glutamine (glutamine phosphoribosyl pyrophosphate amidotransferase) –> 5-phosphoribosylamine (adds first N to PRPP)

conversion of ribose 5’-phosphate to PRPP via PRPP synthetase

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6
Q

First base produced by de novo synthesis of purines

A

inosine mono-phosphate (IMP), which is used to make GMP and AMP by enzymes

failure of enzymes –> autism

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7
Q

Regulation of purine synthesis

A

Activators: PRPP
Inhibitors: AMP, GMP, IMP

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8
Q

Order of pyrimidine synthesis

A

pyrimidine base ring is made and then added to the sugar

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9
Q

Key regulated step in pyrimidine synthesis

A

2 ATP + CO2 + glutamine (carbamoyl phosphate synthetase II) –> carbamoyl phosphate + glutamate

occurs in the cytosol

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10
Q

Regulation of key step in pyrimidine synthesis

A

activator: PRPP, ATP
Inhibitor: UTP

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11
Q

first nucleotide produced by pyrimidine synthesis

A

uracil mono-phosphate (UMP)

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12
Q

Process of making cytosine (CTP)

A

UMP –> UDP –> UTP (CTP synthase, glutamine) –> CTP + glutamate

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13
Q

Enzymes catalyzing changes in phosphoyrlation states of nucleotides

A

Base-specific nucleoside monophosphate kinases: adenylate kinase, guanylate kinase

Nucleoside diphosphate kinase

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14
Q

Enzyme converting nucleotides to deoxynucleotides

A

ribonucleotide reductase (operates on diphosphates)

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15
Q

regulation of ribonucleotide reductase

A

sensing of concentration of dNTPs.
primary regulation site is active in the presence of ATP, inactive when dATP builds up

substrate specific site is sensitive to specific dNTP concentrations. able to switch between operating on one NDP to another

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16
Q

conversion of U to T

A

UDP –> dUDP (dephosphorylation) –> dUMP (thymidylate synthase) –> dTMP (kinases) –> dTDP –> dTTP

17
Q

degradation of purines

A

remove base from sugar (purine nucleoside phosphorylase) –> free base (hypoxanthine or guanine) –> breakdown to uric acid (via xanthine oxidase as final enzyme) –> excretion in urine

18
Q

degradation of pyrimidines

A

remove base ring from ribose –> base ring opened up –> breakdown to succinyl CoA, Malonyl CoA, and Acetyl CoA

water soluble products –> no problems like uric acid produces

19
Q

SCID

A

mutation in adenosine deaminase (involved in purine degradation) –> buildup of dATP –| ribonucleotide reductase –> decrease in production of dNTPs

affects rapidly proliferating cells (eg: immune cells) –> no immune system (“bubble boy”)

20
Q

Gout

A

buildup of uric acid in the blood as a result of purine degradation pathway.

21
Q

Lesch-Nyhan syndrome

A

X-linked recessive
caused by deficiency in one of the primary enzymes in purine salvage pathway (HGPRT) –> higher rates of de novo purine synthesis –> gout sx, self-mutilating behavior, involuntary mvts

22
Q

Methotrexate and 5-FU mechanism

A

5-FU –| thymidylate synthase –| dTMP from dUMP

methotrexate –| formation of THF –| –| thymidylate synthase

23
Q

6-mercaptorpurine mechanism

A

inhibits AMP synthesis (anti-cancer)

24
Q

Azidothymidine (AZT) mechanism

A

inhibits viral polymerase (anti-HIV)

25
Q

Cytosine arabinoside (araC)

A

targets DNA polymerase (anti-leukeia)

26
Q

Acyclovir mechanism

A

targets viral DNA polymerase and reverse transcriptase (anti-HSV)

27
Q

Acivicin mechanism

A

Gln analog, inhibits nucleotide synthesis (mostly GMP; anti-cancer)

28
Q

Regulation of PRPP synthase

A

activator: Pi
inhibitor: purine ribonucleotides

29
Q

Sources of atoms for purine synthesis

A

glutamine, glycine, aspartate

THF

CO2

30
Q

Derivatives of IMP from purine synthesis

A

GMP, AMP

feedback inhibition –> decreased conversion of IMP to GMP, AMP

31
Q

mechanism of mycophenolic acid

A

reversible, noncompetitive inhibitor of IMP dehydrogenase –| conversion to GMP –> decreased T and B cell synthesis

used to prevent graft rejection

32
Q

Sources of atoms for pyrimidine synthesis

A

CO2, glutamine, aspartate

33
Q

Salvage pathway for purine synthesis

A

hypoxanthine, guanine, adenine + PRPP + (HGPRT or adenine phosphoribosyltransferase) –> IMP, GMP, AMP

DEMS Unit 3 (14 decks)

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