Purine and Pyrimidine Metabolism Flashcards

1
Q

What are the oxidation levels of adenine, guanine, hypoxanthine, xanthine, and uric acid?

A

Adenine = 0
Guanine/Hypoxanthine = 1
Xanthine = 2
Uric acid = 3

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2
Q

Explain PRPP synthetase…

A

Ribose-5-phosphate –> PRPP (purine synthesis)

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3
Q

What step is the committed step in purine synthesis?

A

PRPP –> PRA

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4
Q

Which step has the addition of THF in purine synthesis?

A

PRA –> IMP

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5
Q

Explain ribonucleotide reductase…

A

RNA –> DNA

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6
Q

Explain carbamoyl phosphate synthetase II…

A

Gln –> carbamoyl phosphate (pyrimidine synthesis)

*Committed step

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7
Q

Explain aspartate transcarbamoylase (ATCase)…

A

Carbamoyl phosphate –> carbamoyl aspartate

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8
Q

Explain UMP synthase…

A

Orotate + PRPP –> OMP

OMP –> UMP

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9
Q

What Dx is associated with defects in UMP synthase?

A

Orotic aciduria

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10
Q

Which step has the addition of THF in pyrimidine synthesis?

A

dUMP –> dTMP

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11
Q

What enzyme is targeted to prevent graft rejection by depriving cells of GMP/dGTP? How does it work?

A

IMP dehydrogenase…prevents IMP –> XMP which prevents GMP synthesis and inhibits DNA replication of B and T cells

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12
Q

How do Sulfa Drugs work?

A

Antibacterial that competitively inhibits the enzyme that adds PABA to folate, therefore inhibiting DNA replication in cancer cells

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13
Q

Explain AMP deaminase…

A

AMP –> IMP (purine catabolism)

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14
Q

Explain adenosine deaminase (ADA)

A

Adenosine –> Inosine (purine catabolism)

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15
Q

What are the Dx’s associated with ADA defects?

A

Increased ADA –> hemolytic anemia

Decreased ADA –> SCID

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16
Q

What is SCID?

A

“Bubble Boys”
Defect in ADA –> increased adenosine
Adenosine –> dATP which inhibits ribonucleotide reductase, thus inhibiting DNA synthesis of B and T cells

17
Q

Explain xanthine oxidase…

A

Hypoxanthine –> xanthine (purine catabolism)

Xanthine –> Uric acid (purine catabolism)

18
Q

What drug is used to inhibit xanthine oxidase and what Dx does it relieve?

A

Allopurinol…relieves Gout

19
Q

What Dx is associated with increased uric acid production?

A

Gout

20
Q

Explain uridine phosphorylase…

A

Deoxyuridine/Uridine –> uracil (pyrimidine catabolism)

Deoxythymidine –> thymine (pyrimidine catabolism)

21
Q

Explain APRT…

A

Adenine + PRPP –> AMP (purine salvage pathway)

22
Q

Explain HGPRT…

A

Guanine/Hypoxanthine + PRPP –> GMP/IMP (purine salvage pathway)

23
Q

What Dx is associated with defects in HGPRT?

A

Increased uric acid (Lesch-Nyhan syndrome)

24
Q

Explain uridine phosphorylase…

A

Uracil –> uridine (pyrimidine salvage)

25
Q

Explain uridine kinase…

A

Uridine –> UMP (pyrimidine salvage)

26
Q

Explain thymidine phosphorylase…

A

thymine –> deoxythymidine (pyrimidine salvage)

27
Q

Explain thymidine kinase…

A

Deoxythimidine –> dDMP (pyrimidine salvage)

28
Q

What are the 2 Dx that cause Gout and what kind of diet triggers gout?

A

Primary hyperuricemia - over production of uric acid
Secondary hyperuricemia - under excretion of uric acid
Diet - high in meat, seafood, beer

29
Q

What is Lesch-Nyhan syndrome?

A

Defect in HGPRT leading to primary hyperuricemia.

PRPP not used in salvage pathway so used for purine synthesis leading to retardation and self-mutilation

30
Q

What is Acyclovir used for?

A

Antiviral that resembles guanine.

Incorporated into viral DNA to inhibit DNA replication