section 27.9
Biosynthesis of Pyrimidine Nucleotides
S-Adenosyl-L-homocysteine (SAH)
R=- 02C-CH-CH2
-C H -
NH3 +
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
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
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