CLINICAL CASES
397
[43.2]
B. Uric acid has a pKa of 5.4 and is ionized in the body to form urate.
Urate is not very soluble in an aqueous environment, and the quantity
of urate in human blood is very close to the solubility range.
Therefore, situations that lead to excessive degradation of purine
bases can increase the urate concentration past the solubility point
and lead to the formation of urate crystals. The decreased body tem-
perature found in the joints contributes to the formation of urate crys-
tals under these conditions.
[43.3]
B. Lesch-Nyhan syndrome results from an inherited deficiency in
HGPRT. This syndrome is associated with mental retardation and
self-destructive behavior, which may be associated with inadequate
production of purine nucleotides through the salvage pathway in cer-
tain neuronal cells. In addition, Lesch-Nyhan patients have gout
resulting from the inability to salvage purine bases, which leads to
increased levels of uric acid. However, most patients with gout do not
have a defect in HGPRT but have hyperuricemia resulting from a
number of factors, including diet.
B IO C H E M IS T R Y PE A R L S
Purine bases are used in many important biologic processes includ-
ing the formation of nucleic acids.
Because urate is not very soluble in an aqueous environment and the
concentration of urate in human blood is very close to saturation,
conditions that lead to excessive degradation of purine bases can
lead to the formation of urate crystals.
Allopurinol is an inhibitor of xanthine oxidase enzymatic activity.
Colchicine inhibits microtubule formation and prevents phagocytic
cells from engulfing the urate crystals.
REFERENCES
Becker MA. Hyperuricemia and gout. In: Scriver CR, Beaudet AL, Sly WS, et al.,
eds. The Metabolic and Molecular Basis of Inherited Disease, 8th ed. New York:
McGraw-Hill, 2001:2513-35.
Marks DB, Marks AD, Smith CM, eds. Basic Medical Biochemistry. Baltimore,
MD: Lippincott Williams & Wilkins, 1996:633-5.
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