• In humans, uric acid is the end p

• In humans, uric acid is the end product of the degradation of purines. It
serves no known physiologic purpose and is regarded as a waste product.
The size of the urate pool is increased severalfold in individuals with gout.
This excess accumulation may result from either overproduction or
underexcretion.
• The purines from which uric acid is produced originate from three
sources: dietary purine, conversion of tissue nucleic acid to purine nucleotides,
and de novo synthesis of purine bases.
• Abnormalities in the enzyme systems that regulate purine metabolism may
result in overproduction of uric acid. An increase in the activity of
phosphoribosyl pyrophosphate (PRPP) synthetase leads to an increased
concentration of PRPP, a key determinant of purine synthesis and thus
uric acid production. A deficiency of hypoxanthine–guanine phosphoribosyl
transferase (HGPRT) may also result in overproduction of uric acid.
HGPRT is responsible for the conversion of guanine to guanylic acid and
hypoxanthine to inosinic acid. These two conversions require PRPP as the
cosubstrate and are important reutilization reactions involved in nucleic
acid synthesis. A deficiency in the HGPRT enzyme leads to increased
metabolism of guanine and hypoxanthine to uric acid and more PRPP to
interact with glutamine in the first step of the purine pathway. Complete
absence of HGPRT results in the childhood Lesch-Nyhan syndrome,
characterized by choreoathetosis, spasticity, mental retardation, and markedly
excessive production of uric acid.
• Uric acid may also be overproduced as a consequence of increased
breakdown of tissue nucleic acids, as with myeloproliferative and lymphoproliferative
disorders. Cytotoxic drugs used to treat these disorders can