Nucleotide Metabolism

Question 1

Nucleoside vs. Nucleotide

Answer 1

Nucleoside: base + sugar
Nucleoside: base + sugar + phosphate

Question 2

Purines

Answer 2

AMP, GMP, IMP, XMP

Question 3

Pyrimidines

Answer 3

CMP, UMP, TMP

Question 4

Sources of purine bases (5)

Answer 4

Gln, Asp, Gly, CO2, formyl THF

Question 5

Sources of pyrimidine rings (5)

Answer 5

Gln, Asp, N5, HCO3-, methylene THF.

Question 6

Overall de novo synthesis of purines (to IMP)

Answer 6

R5P —> PRPP (PRPP synthetase) —> PRA (GPRPPAT) —> x9 (methotrexate inhibits) —> IMP

Question 7

Overall de novo synthesis of purines (post IMP)

Answer 7

—> adenylosuccinate monophosphate (adenylosuccinate synthetase) —> AMP (adenylosuccinase)

—> xanthosine phosphate (IMP DH) —>GMP (GMP synthetase)

Question 8

Methotrexate MOA

Answer 8

Similar structure to folic acid. Binds competitively to same enzymes to disrupt DNA replication in rapidly dividing cells.

Question 9

Sulfa drugs

Answer 9

Only affects bacteria. They are competitive inhibitors of bacterial enzyme that incorporates PABA into folate and disrupts DNA replication.

Question 10

Salvage pathway enzymes for purine synthesis

Answer 10

HGPRT (guanine)

APRT (adenine)

Question 11

Committed step for pyrimidine synthesis

Answer 11

Formation of n-carbamoyl aspartate (

Question 12

Overall de novo synthesis of pyrimidines (to UMP)

Answer 12

Gln —> carbamoyl phosphate (carb phosphate synthetase II) —> carb aspartate (asp transcarbamoylase) —> dihydroorotate (dihydroorotatase) to the mitochondria —> orotate leave mitochondria —> OMP (UMP synthase —> UMP (UMP synthase)

Question 13

Overall de novo synthesis of pyrimidines (post UMP)

Answer 13

UMP –> UDP
UDP —> UTP —> CTP (CTP synthase)
UDP —> dUMP —> dTMP (thymidylate synthase) -> -> dTTP

Question 14

5-fluorouracil (adrucil)

Answer 14

Mechanism unclear but it likely block the action of thymidylate synthase (no formation of TMP)

Question 15

Orotic aciduria

Answer 15

UMP synthase defective. Orotate cannot become OMP –> UMP.

Can cause anemia and developmental delays.

Question 16

Acyclovir

Answer 16

Resembles guanine, but not recognized by thymidine kinase. DNA replication halted.

Question 17

GMP Catabolism

Answer 17

Becomes xanthine —> uric acid (xanthine oxidase)

Question 18

AMP, IMP, Adenosine Catabolism

Answer 18

—> inosine (adenosine deaminase) —> hypoxanthine (PNP) —> xanthine (xanthine oxidase) —> uric acid (xanthine oxidase)

Question 19

ADA (adenosine deaminase) problems

Answer 19

Overproduction: causes hemolytic anemia (premature destruction of RBCs)
Underproduction: severe combined immunodeficiency (SCID)

Question 20

C and U catabolism

Answer 20

—> uridine —> uracil —> b-alanine —> malonyl CoA (to FAS)

Question 21

T catabolism

Answer 21

—> thymine —> b-aminoisobtyrate —> methylmathonyl CoA and succinyl CoA (to TCA)

Question 22

Inhibition of APRT causes:

Answer 22

Kidney stones

Question 23

Inhibition of HGPRT causes:

Answer 23

Lesch-Nyhan syndrome

Question 24

Lesch-Nyhan syndrome

Answer 24

Defective HGPRT
Overproduce uric acid –> gout
Can have kidney stones, poor muscle control, mental retardation and self mutilation.