section 27.9

Biosynthesis of Pyrimidine Nucleotides

637

— RSH

S-Adenosyl-L-homocysteine (SAH)

Deoxyadenosine

Ketosugar

(Unstable

intermediate)

Ad=Adenine;

R=- 02C-CH-CH2

-C H -

NH3 +

(b)

F IG U R E 2 7 -2 3

Mechanism of action of S-adenosylhomocysteine hydrolase (enzyme) and its inhibition by deoxyadenosine. (a) The

enzyme uses enzyme-bound NAD+ to temporarily oxidize substrate and eventually hydrolyze it to adenosine and

homocysteine. [Reproduced with permission from R. H. Abeles, Suicide enzyme inactivators.

Chem. Eng. News

61(38),

55 (September 19, 1983). ©1983 by the American Chemical Society.] (b) Deoxyadenosine, a suicide substrate, is also

oxidized by the enzyme with the formation of a ketosugar, which undergoes decomposition, with the product

dissociating from the enzyme and leaving the enzyme in the reduced state (NADH).

nucleotide cycle and leads to muscle dysfunction

during exercise; however, the cycle operates

minimally at rest so that AMP deaminase deficiency

should not cause muscle dysfunction during rest. Type

F IG U R E 2 7 -2 4

Purine nucleotide. The cycle plays an important role in energy production

in skeletal muscle during exercise.

lia (fast-twitch oxidative) and type I (slow-twitch

oxidative) muscle fibers have greater oxidative

capacity and are less dependent on the cycle than type

lib (fast-twitch glycolytic) fibers. Thus, gradual

exercise programs that lead to production of a greater

proportion of type Ha and type I fibers might improve

exercise tolerance in AMP deaminase deficiency.

Xanthine Oxidase Deficiency

This autosomal recessive trait results in hypouricemia and

in increased urinary excretion of hypoxanthine and xan-

thine. Patients frequently have xanthine stones.

27.9 Biosynthesis of Pyrimidine Nucleotides

Pyrimidine nucleotides, in common with purine nu-

cleotides, are required for the synthesis of DNA and RNA.

They also participate in intermediary metabolism. For ex-

ample, pyrimidine nucleotides are involved in the biosyn-

thesis of glycogen (Chapter 15) and of phospholipids