Nucleotide Metabolism

Question 1

What is the difference between nucleotides and nucleosides?

Answer 1

Nucleotides = base + sugar + phosphate

Nucleosides = base + sugar

Question 2

Describe the structure of Adenosine Triphosphate (ATP)

Answer 2

Base = adenine

Sugar = ribose

Phosphate groups = alpha, beta, gamma

Question 3

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

Answer 3

N-glycosidic bond

Question 4

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

Answer 4

Ribonucleotide reductase (also requires NADPH)

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

Question 5

What is the nucleoside form of adenine?

Answer 5

Adenosine

Question 6

What is the nucleoside form of guanine?

Answer 6

Guanosine

Question 7

What is the nucleoside form of xanthine?

Answer 7

Xanthosine

Question 8

What is the nucleoside form of hypoxanthine?

Answer 8

Inosine

Question 9

What is the nucleoside form of cytosine?

Answer 9

Cytidine

Question 10

What is the nucleoside form of uracil?

Answer 10

Uridine

Question 11

What is the nucleoside form of thymine?

Answer 11

Thymidine

Question 12

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

Answer 12

Catabolic; ETC

PPP; anabolic

Question 13

How does NADPH function in drug metabolism in the liver?

Answer 13

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

Question 14

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

Answer 14

Glutathione reductase activity

Question 15

What are the 2 primary products of the PPP?

Answer 15

NADPH and ribose 5 phosphate

Question 16

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

Answer 16

D. All of the above

Question 17

Purine catabolism is an __________ process

Answer 17

Oxidative

Question 18

What is the mechanism of action of methotrexate?

Answer 18

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

Question 19

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

Answer 19

Sugar (alpha-D-ribose-5P)

Question 20

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

Answer 20

PRPP to PRA

Enzyme = glutamine:phosphoribosyl pyrophosphate amidotransferase

Question 21

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

Answer 21

PRPP synthetase (utilizes ATP)

Question 22

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

Answer 22

IMP (inosine monophosphate)

Question 23

What are the 2 salvage pathway enzymes for purine biosynthesis?

Answer 23

HGPRT

APRT

Question 24

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

Answer 24

Fumarate

Question 25

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

Answer 25

(+) PRPP | -) purine nucleotides (GMP, AMP, IMP

Question 26

What enzyme is directly targeted by methotrexate via competitive inhibition?

Answer 26

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

Question 27

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

Answer 27

GTP; ATP

Question 28

What is the initial building block in pyrimidine nucleotide synthesis?

Answer 28

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

Question 29

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?

Answer 29

5-fluorouracil (inhibits thymidylate synthase)

Question 30

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?

Answer 30

UMP

Question 31

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

Answer 31

Aspartate transcarbamoylase - Yes this is the rate limiting step

Question 32

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

Answer 32

Carbamoyl phosphate synthetase II (+) PRPP (-) UTP

Question 33

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

Answer 33

Phase I: Fabrication of orotate ring Phase II: attach PRPP to form UMP Phase III: convert UMP to uridine, cytosine, and thymidine

Question 34

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

Answer 34

Orotic aciduria

Question 35

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

Answer 35

Thioredoxin (ribonucleotide reductase)

Question 36

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?

Answer 36

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

Question 37

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

Answer 37

Acyclovir

Question 38

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?

Answer 38

Sulfa drugs

Question 39

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

Answer 39

Deoxyribonuclease (would be ribonuclease for RNA)

Question 40

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

Answer 40

Phosphodiesterase

Question 41

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

Answer 41

Nucleotidases

Question 42

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

Answer 42

Nucleosidase

Question 43

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?

Answer 43

Xanthine oxidase

Question 44

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.

Answer 44

Hemolytic anemia SCID

Question 45

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

Answer 45

Malonyl CoA = ketogenic (from UMP and CDP) Methylmalonyl CoA and Succinyl CoA = glucogenic (from dTDP)

Question 46

Compare the subcellular location of purine synthesis vs. pyrimidine synthesis

Answer 46

Purine synthesis takes place in the cytosol Pyrimidine synthesis takes place in the cytosol and mitochondria

Question 47

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

Answer 47

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

Question 48

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

Answer 48

B; T; X Adenosine

Question 49

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

Answer 49

APRT HGPRT