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EoM 2 > Nucleotide Metabolism > Flashcards

Nucleotide Metabolism Flashcards

1
Q

Which amino acid is an important precursor for de novo synthesis of nucleotides?

A

glutamine

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2
Q

What is the first step in purine de novo synthesis?

A

alpha-D-Ribose 5-phosphate to Phosphoribosyl pyrophosphate (PRPP)

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3
Q

What enzyme synthesizes the first step in purine de novo synthesis?

A

PRPP Synthetase

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4
Q

What cofactor does PRPP Synthetase need?

A

ATP

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5
Q

What is the second step of purine de novo synthesis?

A

A glutamine and water is added to PRPP, resulting in 5-Phospho-beta-d-ribosylamine

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6
Q

What enzyme catalyzes the addition of glutamine and water to PRPP?

A

PRPP Glutamyl Amidotransferase

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7
Q

Which enzyme adds a formyl group in purine de novo synthesis?

A

Formyltransferase

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8
Q

What is the donor to formyltransferase and what is left over?

A

Donor is 10-formyltetrahydrofolate and what’s left is tetrahydrofolate

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9
Q

Adenylosuccinate synthetase is the second to last step in de novo synthesis of adenosine monophosphate (purine). What does it require?

A

GTP, Mg2+

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10
Q

Transamidinase is the last step in de novo synthesis of guanosine monophosphate (purine). What does it require?

A

ATP, Glutamine

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11
Q

What do ADP and GDP inhibit in purine de novo synthesis?

A

PRPP synthetase

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12
Q

What do GMP, IMP, and AMP collectively inhibit in purine de novo synthesis?

A

PRPP glutamyl amidotransferase

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13
Q

Which enzyme converts ribonucleoside diphosphate to 2’-deoxyribonucleoside diphosphates?

A

Ribonucleotide reductase

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14
Q

What reaction “recharges” the ribonucleoside to deoxyribonucleoside conversion?

A

Thioredoxin reductase, NADPH and H+

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15
Q

Which enzyme salvages AMP from adenine?

A

Adenine phosphoribosyl transferase

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16
Q

Which enzyme converts hypoxanthine to IMP and guanine to GMP? (Purine salvage)

A

Hypoxanthine-guanine phosphoribosyl transferase (HGPRT)

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17
Q

What do both purine salvage pathways need as an input?

A

PRPP

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18
Q

Multi-reaction enzyme complex at the start of pyrimidine de novo synthesis?

A

“CAD”

1) Carbamoyl phosphate synthetase II
2) Aspartate transcarbamoylase
3) Dihydroorotase

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19
Q

What downregulates “CAD” in pyrimidine de novo synthesis?

A

UTP and UDP (negative feedback)

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20
Q

What upregulates “CAD” in pyrimidine de novo synthesis?

A

PRPP

21
Q

Where does PRPP appear in pyrimidine de novo synthesis?

A

As an input in the reaction catalyzed by orotate phosphoribosyltransferase

22
Q

Folate’s role in pyrimidine de novo synthesis?

A

Last step forming TMP; thymidilate synthase uses 10-methyltetrahydrofolate and outputs TMP and dihydrofolate.

23
Q

CTP synthetase, the last step before forming CTP, requires what reactants?

A

UTP, ATP, and glutamine

24
Q

Is it the products of purine or pyrimidine metabolism which are insoluble?

A

Purine

25
Q

How does PRPP synthetase factor into coordinated regulation of purine and pyrimidine metabolism?

A

It is inhibited by nucleotide products of both pathways

26
Q

How is pyrimidine biosynthesis regulated by purine biosynthesis (crossregulation)?

A

ATP is necessary for pyrimidine biosynthesis (remember it’s a purine)

27
Q

Which antineoplastic agents are analogs of glutamine, meant to inhibit the pathways and prevent cell division?

A

Azaserine and Acivicin

28
Q

What does 5-fluorouracil do directly in the body?

A

Nothing. It’s a prodrug and must be metabolized into FdUMP first.

29
Q

What is 5-fluorouracil’s (metabolized into FdUMP) mechanism of action

A

Competitive inhibitor of Thymidylate Synthase (normally uses 5,10-Methylenetetrahydrofolate)

30
Q

What does allopurinol do to help in the treatment of gout?

A

Inhibits xanthine oxidase

31
Q

How do methotrexate and aminopterin treat cancer and rheumatoid arthritis?

A

They inhibit dihydrofolate reductase (dihydrofolate conversion to tetrahydrofolate)

32
Q

What PABA analog and competitive inhibitor did we learn about?

A

Sulfonamides

33
Q

What is significant about PABA?

A

Bacteria are able to generate dihydrofolate from it. Competitive inhibition by sulfonamides interferes with folate metabolism.

34
Q

What does trimethoprim, an antibiotic, do?

A

Inhibits dihydrofolate reductase

35
Q

What does 6-mercaptopurine do in the purine salvage pathway?

A

Acts as a competitive inhibitor of Hypoxanthine-guanine phosphoribosyl transferase (HGPRT)

36
Q

What is formed instead of IMP/GMP when 6-mercaptopurine competes with hypoxanthine and guanine as a substrate for HGPRT?

A

TIMP

37
Q

What does HGPRT stand for?

A

Hypoxanthine-guanine phosphoribosyl transferase

38
Q

What is a drug treatment for a regular case of gout (hyperuricemia)?

A

Allopurinol

39
Q

A rare inherited disorder caused by a deficiency of the enzyme HGPRT and causing extreme hyperuricemia

A

Lesch-Nyhan Syndrome (LNS)

40
Q

What can be said about the inheritance pattern of Lesch-Nyhan Syndrome

A

X-linked

41
Q

Glucose-6-phosphatase deficiency characterized by glycogen build up and hyperuricemia

A

von Gierke disease

42
Q

Why does von Gierke disease cause hyperuricemia

A

lt causes chronic lactic acidosis. lactic acid and uric acid compete for the same renal tubular transport mechanism

43
Q

What inherited disorder related to purine metabolism damages the immune system and causes severe combined immunodeficiency (SCID)?

A

Adenosine Deaminase Deficiency

44
Q

Which purine metabolism disorder results in severe deficiency of T cells and immune dysfunction?

A

Purine Nucleoside Phosphorylase Deficiency

45
Q

Autosomal recessive metabolic disorder characterized by neurological problems

A

Dihydropyrimidine dehydrogenase deficiency

46
Q

Orotic Aciduria

A

Disorder involving disorder of orotate phosphoribosyltransferase (Type 1) and Orotidylic acid decarboxylase (Type 1, 2). Characterized by orotic acid build up due to inability to convert to UMP

47
Q

Which two molecules coregulate purine/pyrimidine production?

A

ATP and PRPP

48
Q

Drugs that prevent the production of both purine/pyrimidine synthesis pathways?

A

Azaserine (glutamine analog) and methotrexate (inhibit dihydrofolate reductase)

EoM 2 (12 decks)

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