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MCM BCHE > Nucleotide Metabolism > Flashcards

Nucleotide Metabolism Flashcards

1
Q

What is the difference between nucleotides and nucleosides?

A

Nucleotides = base + sugar + phosphate

Nucleosides = base + sugar

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2
Q

Describe the structure of Adenosine Triphosphate (ATP)

A

Base = adenine

Sugar = ribose

Phosphate groups = alpha, beta, gamma

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3
Q

What type of bond connects the base to the sugar in a nucleotide?

A

N-glycosidic bond

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4
Q

What enzyme is required to go from a nucleotide diphosphate to a 2’ deoxynucleotide diphosphate?

A

Ribonucleotide reductase (also requires NADPH)

[note that this is positively regulated by ATP and negatively regulated by dATP]

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5
Q

What is the nucleoside form of adenine?

A

Adenosine

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6
Q

What is the nucleoside form of guanine?

A

Guanosine

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7
Q

What is the nucleoside form of xanthine?

A

Xanthosine

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8
Q

What is the nucleoside form of hypoxanthine?

A

Inosine

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9
Q

What is the nucleoside form of cytosine?

A

Cytidine

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10
Q

What is the nucleoside form of uracil?

A

Uridine

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11
Q

What is the nucleoside form of thymine?

A

Thymidine

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12
Q

NADH differs from NADPH in that NADPH has an additional phosphate group.

NADH is produced in _________ reactions and is later used in the ______.

NADPH is primarily produced in the oxidative part of the ______ and is used in _________ syntheses, hepatic detoxification (as an antioxidant), and in drug metabolism via CYP450

A

Catabolic; ETC

PPP; anabolic

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13
Q

How does NADPH function in drug metabolism in the liver?

A

Adds an OH group to make the drug a more polar metabolite so that it is more readily absorbed across cell membranes for further breakdown

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14
Q

The production of NADPH and its conversion to NADP+ is coupled to what enzymatic process for protection against oxidative stress?

A

Glutathione reductase activity

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15
Q

What are the 2 primary products of the PPP?

A

NADPH and ribose 5 phosphate

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16
Q

Purine bases are a structural component of which of the following?

A. Coenzyme A
B. NAD+
C. FAD
D. All of the above
E. B and C only
A

D. All of the above

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17
Q

Purine catabolism is an __________ process

A

Oxidative

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18
Q

What is the mechanism of action of methotrexate?

A

Methotrexate inhibits the synthesis of nucleic acids by inhibiting the formation of THF, which is a major carbon-donor for purine and pyrimidine synthesis

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19
Q

What is the initial building block in de novo purine synthesis?

A

Sugar (alpha-D-ribose-5P)

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20
Q

What is the rate limiting step of de novo purine synthesis?

A

PRPP to PRA

Enzyme = glutamine:phosphoribosyl pyrophosphate amidotransferase

21
Q

In de novo purine synthesis, how does alpha-D-ribose-5P become PRPP?

A

PRPP synthetase (utilizes ATP)

22
Q

What purine is converted into either GMP or AMP in de novo purine synthesis?

A

IMP (inosine monophosphate)

23
Q

What are the 2 salvage pathway enzymes for purine biosynthesis?

A

HGPRT

APRT

24
Q

What byproduct of de novo purine synthesis can directly enter the TCA cycle?

A

Fumarate

25
Q

What are the positive and negative regulators on glutamine:phosphoribosyl pyrophosphate amidotransferase (the rate limiting enzyme of de novo purine synthesis)

A

(+) PRPP

-) purine nucleotides (GMP, AMP, IMP

26
Q

What enzyme is directly targeted by methotrexate via competitive inhibition?

A

Dihydrofolate reductase (DHFR), which is responsible for reducing dihydrofolic acid to tetrahydrofolic acid (THF) using NADPH as an electron donor

27
Q

Cross regulation of purine nucleotide biosynthesis means that AMP synthesis is stimulated by ______, while GMP synthesis is stimulated by _______

A

GTP; ATP

28
Q

What is the initial building block in pyrimidine nucleotide synthesis?

A

The base (as opposed to the sugar in de novo purine synthesis)

29
Q

Methotrexate is a commonly utilized anticancer agent that inhibits THF formation in purine biosynthesis. What common anticancer agent is utilized in a similar way in pyrimidine biosythesis?

A

5-fluorouracil (inhibits thymidylate synthase)

30
Q

Pyrimidines include C, U, and T. What is the first pyrimidine to be formed in de novo pyrimidine synthesis that can then be further converted into the other two?

A

UMP

31
Q

What enzyme is responsible for converting cabamoyl phosphate to carbamoyl aspartate in de novo synthesis of pyrimidines? Is this the rate limiting step?

A

Aspartate transcarbamoylase - Yes this is the rate limiting step

32
Q

What enzyme is responsible for synthesizing carbamoyl phosphate in order to begin the process of pyrimidine biosynthesis? What are its positive and negative regulators?

A

Carbamoyl phosphate synthetase II

(+) PRPP

(-) UTP

33
Q

In general, what are the 3 phases of de novo pyrimidine synthesis?

A

Phase I: Fabrication of orotate ring

Phase II: attach PRPP to form UMP

Phase III: convert UMP to uridine, cytosine, and thymidine

34
Q

What hereditary disorder is associated with the process of de novo pyrimidine synthesis and is typically treated using oral uridine?

A

Orotic aciduria

35
Q

Deoxyribonucleotides are formed from ribonucleotides. The hydrogen donor = reduced ___________

A

Thioredoxin (ribonucleotide reductase)

36
Q

What clinical condition is characterized by a mutation in HGPRT leading to allosteric activation of glutamine:phosphoribosyl pyrophosphate amidotransferase by PRPP, making PRPP available for more purine synthesis?

A

Lesch-Nyhan Syndrome

[clinical presentation includes urate kidney stones, gout, poor muscle control, mental retardation, self-mutilation]

37
Q

What drug is used to heal chickenpox and herpes lesions by inhibiting viral enzymes for DNA synthesis?

A

Acyclovir

38
Q

What type of drugs act as competitive inhibitors of the bacterial enzyme that incorporates p-aminobenzoic acid (PABA) into folate, thus disrupting DNA replication selectively in bacteria?

A

Sulfa drugs

39
Q

What enzyme is required to convert a long DNA chain into short oligomers?

A

Deoxyribonuclease (would be ribonuclease for RNA)

40
Q

What enzyme is required to convert short DNA oligomers into NMPs or dNMPs?

A

Phosphodiesterase

41
Q

What enzyme is required to convert NMPs or dNMPs into nucleosides and deoxynucleosides?

A

Nucleotidases

42
Q

What enzyme is required to remove ribose group and convert into pyrimidine and purine base?

A

Nucleosidase

43
Q

Allopurinol is a preventative treatment for gout, which may result from a dysfunction in the purine nucleotide catabolism pathway. What specific enzyme does allopurinol inhibit?

A

Xanthine oxidase

44
Q

Adenosine deaminase is required to convert adenosine to inosine in purine nucleotide catabolism. ____________ may result from excess adenosine deaminase, while ________ may result from a deficiency of this enzyme.

A

Hemolytic anemia

SCID

45
Q

What are the 3 possible end products of pyrimidine nucleotide catabolism? Are they glucogenic or ketogenic?

A

Malonyl CoA = ketogenic (from UMP and CDP)

Methylmalonyl CoA and Succinyl CoA = glucogenic (from dTDP)

46
Q

Compare the subcellular location of purine synthesis vs. pyrimidine synthesis

A

Purine synthesis takes place in the cytosol

Pyrimidine synthesis takes place in the cytosol and mitochondria

47
Q

Which nucleotide is more expensive to make, purines or pyrimidines?

A

Purines, because they require 4 ATP to generate IMP while only 3 ATP are required to generate UMP

48
Q

SCID involves defective ______ and _____ cells. It is an ___-linked disorder, so most patients are male.

Patients end up with a buildup of __________, and thus impaired DNA synthesis and a compromised immune system

A

B; T; X

Adenosine

49
Q

In terms of purine salvage, defects in _________ lead to renal lithiasis, while defects in _______ lead to excess uric acid production

A

APRT

HGPRT

MCM BCHE (13 decks)

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