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metabolism > Purine & pyrimidine metabolism > Flashcards

Purine & pyrimidine metabolism Flashcards

1
Q

Is the purine built on top of ribose or attached to it?

A

Made on top of it

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2
Q

What is the first formal step in the formation of purines?

A

Activation of the ribose, which forms 5-phospho-alpha-D-ribose-1-pyrophosphoric acid (PRPP)

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3
Q

What gives the pyrophosphate group to PRPP?

A

ATP

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4
Q

What is the second step in the formation of purines?

A

Formation of 5-phosphoribosylamine, with the amine group coming from glutamine

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5
Q

What is the regulated step in purine biosynthesis?

A

Formation of 5-phosphoribosylamine, catalyzed by glutamine PRPP amidotransferase

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6
Q

Nucleotide IMP

A

Formed by step 11 in purine synthesis, which is a precursor for both GTP and ATP

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7
Q

What is the enzyme catalyzing the formation of PRPP?

A

Ribosephosphate pyrophosphokinase

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8
Q

Why is tumor treatment by purine synthesis inhibition helpful?

A

Tumor cells are more affected by a disruption in de novo synthesis of purines; others rely more on recycling of purines

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9
Q

6-mercaptopurine

A

Converted to a nucleotide by the purine salvage pathway, then inhibiting the enzymes in the purine synthesis pathway, including glutamine PRPP amidotransferase

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10
Q

What is the regulated step in pyrimidine synthesis?

A

Formation of carbamoyl phosphate, catalyzed by carbamoyl phosphate synthetase II

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11
Q

Is the pyrimidine ring formed on top of ribose-5P or is it attached afterward?

A

Attached after

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12
Q

Precursor for synthesis of other pyrimidines

A

UMP

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13
Q

Leflunomide

A

Rheumatoid arthritis drug that blocks the formation of pyrimidines by inhibition of dihydroorotate dehydrogenase

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14
Q

How is dTMP made?

A

By conversion of dUMP through thymidylate synthase

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15
Q

5-fluorouracil

A

Becomes f-dUMP, which is an inhibitor of thymidylate synthase and blocks dTMP formation. Used as anticancer agent

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16
Q

Methotrexate

A

Blocks the reduction of dihydrofolate back to tetrahydrofolate, which is necessary for the reaction of thymidylate synthase. In the presence of methotrexate, thymidylate sythase is nonfunctional due to overaccumulation of DHF

17
Q

Ribonucleotide reductase

A

Acts on ribonucleotide-5-diphosphates (ADP, GDP, UDP, CDP) to make corresponding deoxyribonucleotide

18
Q

What happens in the reaction catalyzed by ribonucleotide reductase?

A

The 2’-OH is replaced with a hydrogen

19
Q

What factors are needed in the reaction catalyzed by ribonucleotide reductase?

A

Thioredoxin

20
Q

What enzymes are upregulated during the S phase of the cell cycle?

A

Ribonucleotide reductase and thymidylate synthase

21
Q

Order of degradation of DNA/RNA

A

DNA/RNA -> nucleotides -> nucleosides -> bases

22
Q

What is the order of enzymes needed to catalyze breakdown of DNA/RNA?

A

Nucleases, nucleotidases, nucleoside phosphorylases

23
Q

What does adenine become after degradation?

A

Hypoxanthine

24
Q

What percentage of purines are recycled after use?

A

90%

25
Q

What is the enzyme needed in the purine salvage pathway?

A

Hypoxanthine-guanine phosphoribosyltransferase (HGPRTase)

26
Q

Genetic deficiency in HGPRTase

A

Results in Lesch-Nyhan syndrome, characterized by mental retardation and self-mutilation

27
Q

What percentage of purines are not reused, and what do they become?

A

10%; uric acid

28
Q

What is the enzyme catalyzing the reaction of purines to uric acid?

A

Xanthine oxidase

29
Q

What are the bases attached to in the reaction catalyzed by HGPRTase?

A

PRPP

30
Q

What are the two forms of uric acid, and which one can form urate?

A

Keto form and enol form; enol form can be deprotonated to become urate

31
Q

Where is urate more abundant? Uric acid?

A

Urate: blood

Uric acid: urine

32
Q

What happens when there is overproduction or underexcretion of gout?

A

Uric acid builds up in the body. Stored in joint spaces, causing gout; crystallized in kidney tubules, causing kidney stones.

33
Q

Allopurinol

A

Inhibitor of xanthine oxidase: prevents overproduction of uric acid, treating gout

metabolism (21 decks)

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