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CBFM - M1T1 > Nucleotide Metabolism > Flashcards

Nucleotide Metabolism Flashcards

1
Q

What drug inhibits synthesis of guanine nucleotides by competitively inhibiting the IMP dehydrogenase?

A

Mycophenolate & Ribavarin

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2
Q

What causes gout?

A

Overproduction or under-excretion of uric acid due to enzyme deficiency

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3
Q

How does gout differ from Lesch-Nyhan Syndrome?

A

Gout has many causes, one of which is a partial mutation in the Hypoxanthine-Guanine Phosphoribosyl Transferase (HGPRT) of purine salvage. Lesch-Nyhan syndrome is caused by a deficiency of HGPRT causing overproduction of purines de novo and increased uric acid. Symptoms include hyperuricemia, megaloblastic anemia, cognitive deficits, behavioral problems, and self-mutilation

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4
Q

The UMP synthase is a bifunctional protein with 2 catalytic domains. What molecule does the synthase synthesize and how?

A

Synthesizes UMP by combining Orotic Acid & PRPP

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5
Q

What molecule is the parent of purines?

A

IMP

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6
Q

What enzyme is responsible for GDP/GTP synthesis from IMP?

A

IMP dehydrogenase

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7
Q

What is the mechanism of action of Sulfonamides?

A

Inhibit folate synthesis to prevent synthesis of purines and thymidine

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8
Q

What is the committed step of purine synthesis?

A

Amidophosphoribosyl transferase

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9
Q

What step in pyrimidine synthesis is rate limiting? How is the step regulated?

A

Synthesis of carbamoyl phosphate by the Carbamoyl Phosphate Synthetase II. The enzyme is activated by ATP & PRPP and inhibited by UDP/UTP.

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10
Q

What is Fluorouracil? What is its function?

A

Pyrimidine analog that inhibits the thymidylate synthase to block dTMP synthesis

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11
Q

What molecule donates a methyl group to dUMP to synthesize dTMP?

A

N5, N10-Tetrahydrofolate

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12
Q

What drug inhibits the ribonucleotide reductase to decrease synthesis of deoxyribonucleotides?

A

Hydroxyurea

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13
Q

How is kidney stone formation associated with purine metabolism?

A

Deficiency of the Adenine Phosphoribosyl Transferase (APRT) in purine base salvage causes kidney stone development

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14
Q

What are the four enzymes involved in purine synthesis?

A

PRPP Synthetase, Amidophosphoribosyl transferase, Adenylosuccinate synthetase, IMP dehydrogenase

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15
Q

Briefly summarize purine catabolism.

A

GMP/AMP are broken down into guanine/adenosine by the guanosine/adenosine deaminase, respectively, to form xanthine. The xanthine oxidase then converts xanthine to uric acid for excretion in the urine.

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16
Q

What are the products of pyrimidine degradation?

A

B-alaine & B-aminoisobutyrate - Carbon skeletons can enter TCA

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17
Q

What vitamins play a role in 1-Carbon Metabolism?

A

Vitamins B6, B12, & Folate

18
Q

What molecule is a common intermediate in the de novo synthesis of both purines and pyrimidines?

A

PRPP

19
Q

How is the rate of purine synthesis controlled?

A

Purine synthesis is controlled by the concentration of PRPP. High PRPP increases the rate of synthesis

20
Q

What enzyme in pyrimidine synthesis is allosterically regulated by CTP (inhibited) and ATP (activated)?

A

Aspartate Transcarbamoylase to form Carbamoyl Aspartic Acid (CAA)

21
Q

What molecule is the parent of pyrimidines?

A

OPP

22
Q

What drug inhibits the DHF reductase to limit THF availability and inhibit dTMP synthesis?

A

Methotrexate - treats rheumatoid arthritis, psoriasis, cancer

23
Q

What is the function of Allopurinol?

A

Inhibits the xanthine oxidase to prevent uric acid synthesis for gout treatment

24
Q

How is acute gout treated?

A

With anti-inflammatory agents, such as Colchicine

25
Q

What is Orotic Aciduria? How is the disease caused?

A

Defect of the UMP synthase causing orotic aciduria, megaloblastic anemia, growth failure, developmental delays, and immune defect. NH4+ levels remain unchanged.

26
Q

What is the process of pyrimidine base salvage?

A

Free bases are converted to nucleosides by a non-specific nucleoside phosphorylase. A nucleoside-specific kinase converts the nucleoside to a nueclotide.

27
Q

How is CTP synthesized?

A

CTP is synthesized from UTP by the CTP Synthase

28
Q

How is dTMP synthesized?

A

UDP is converted to dUDP by the ribonucleotide reductase. Though 1-Carbon metabolism & the Thymidylate synthase, dUMP is converted to dTMP.

29
Q

What is the function of Leflunomide?

A

Reversibly inhibits UMP synthesis to treat arthritis

30
Q

The PRPP Synthetase synthesizes PRPP from Ribose-5-Phosphate. How is this enzyme regulated?

A

Activated by phosphate and inhibited by purine nucleotides (GDP, ADP)

31
Q

What is the function of 6-Mercaptopurine?

A

Purine analog that competes for binding to HGPRT and inhibits reactions involving IMP to prevent purine synthesis

32
Q

What group of nitrogenous bases are these?

A

Purines - Adenine & Guanine

33
Q

De novo purine and pyrimidine synthesis both utilize CO2, Aspartate, & Glutamine. What additional molecules are needed for pyrimidine synthesis?

A

Glycine & Formate

34
Q

What enzyme is responsible for ADP/ATP synthesis from IMP?

A

Adenylosuccinate synthetase

35
Q

What is Severe Combined Immunodeficiency (SCID)?

A

SCID is caused by deficiencies in the adenosine deaminase. ATP building up in cells leads to apoptosis of B, T, & NK cells.

36
Q

What is Von Gierke’s Disease?

A

Deficiency in the glucose-6-phosphatase of the PPP that results in gout

37
Q

What group of nitrogenous bases are these?

A

Pyrimidines - Thiamine & Cytosine

38
Q

What is the function of the ribonucleotide reductase?

A

Reduces the ribose sugar to deoxyribose

39
Q

What enzymes are responsible for purine base salvage?

A

Adenine Phosphoribosyl Transferase (APRT)
Adenine –> AMP

Hypoxanthine-Guanine Phosphoribosyl Transferase (HGPRT)
Hypoxanthine –> IMP
Guanine –> GMP

40
Q

How does a nucleoside differ from a nucleotide?

A

A nucleoside is only the nitrogenous base attached to a sugar. Nucleotide refers to the nitrogenous base, sugar, and phosphate group

CBFM - M1T1 (42 decks)

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