section 27.8

Catabolism of Purine Nucleotides

629

O

,

Xanthine

oxidase

HN

V

\

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,

Biochemistry,

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