section 27.8
Catabolism of Purine Nucleotides
Uric acid
F IG U R E 2 7 -1 4
Pathways for the formation of uric acid from purine nucleotides. [Reproduced with permission from G. Zubay,
2nd ed. New York: (Macmillan 1988). © 1988 by Macmillan Publishing Company.]
liver and is present in most tissues. The products of the
xanthine oxidase reaction are uric acid and hydrogen per-
oxide. In primates (humans included) and birds, uric acid
is excreted in the urine. In mammals other than primates,
a liver enzyme, urate oxidase, converts uric acid to allan-
toin (Figure 27-15). In lower animals, allantoin is metab-
olized to allantoic acid (some fish), urea (most fish and
amphibia), and ammonia (some marine invertebrates and
crustaceans). In humans, uric acid, urea, and creatinine
are the end products of nitrogen metabolism. All three
are excreted in urine. The primary end product is urea
(Chapter 17). Animals in which uric acid is the major end
product excrete the rather insoluble uric acid as a semisolid
mass, which allows for conservation of water. In humans,
uric acid production and excretion is a balanced process.
On a daily basis, about two-thirds of the uric acid produced
is excreted by the kidneys and the remainder via intestinal
bacterial degradation. In chronic renal failure and hype-
ruricemia, extrarenal uric acid disposal is enhanced. Re-
nal excretion of uric acid is a multicomponent bidirec-
tional process involving glomerular filtration (
1 0 0
%) and
proximal tubular reabsorption (98-100%), followed by
proximal tubular secretion (50%) and proximal tubular
reabsorption (40—44%). Ultimately, the renal clearance
of uric acid is only about 7-10% of creatinine clearance
(Chapter 17).
Xanthine Oxidase Reaction
Xanthine oxidase is a flavoprotein that contains molyb-
denum, nonheme iron, and labile sulfur. The enzyme is
present in two forms, one with dehydrogenase activity
(xanthine dehydrogenase) and the other with oxidase ac-
tivity. The former is converted to the latter by oxidation of
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