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Flashcards in Nucleotide Metabolism Deck (24):
1

Nucleoside vs. Nucleotide

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

2

Purines

AMP, GMP, IMP, XMP

3

Pyrimidines

CMP, UMP, TMP

4

Sources of purine bases (5)

Gln, Asp, Gly, CO2, formyl THF

5

Sources of pyrimidine rings (5)

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

6

Overall de novo synthesis of purines (to IMP)

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

7

Overall de novo synthesis of purines (post IMP)

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

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

8

Methotrexate MOA

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

9

Sulfa drugs

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

10

Salvage pathway enzymes for purine synthesis

HGPRT (guanine)
APRT (adenine)

11

Committed step for pyrimidine synthesis

Formation of n-carbamoyl aspartate (

12

Overall de novo synthesis of pyrimidines (to UMP)

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)

13

Overall de novo synthesis of pyrimidines (post UMP)

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

14

5-fluorouracil (adrucil)

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

15

Orotic aciduria

UMP synthase defective. Orotate cannot become OMP --> UMP.
Can cause anemia and developmental delays.

16

Acyclovir

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

17

GMP Catabolism

Becomes xanthine ---> uric acid (xanthine oxidase)

18

AMP, IMP, Adenosine Catabolism

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

19

ADA (adenosine deaminase) problems

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

20

C and U catabolism

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

21

T catabolism

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

22

Inhibition of APRT causes:

Kidney stones

23

Inhibition of HGPRT causes:

Lesch-Nyhan syndrome

24

Lesch-Nyhan syndrome

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