Review
Physiology and pharmacology
Uric acid largely exists as urate (the ionized form, pKa is
5.8) at neutral pH. It is the end product of purine metabolism
in humans. High serum levels of urate (hyperuricaemia)
are causative in gout and urolithiasis, due to the formation
and deposition of monosodium urate crystals. Urate is singly
charged at neutral pH and at a concentration of 6.8 mg/
dL (0.40 mmol/L) in human serum, crystals can form spontaneously.
The solubility of urate decreases with increasing
local sodium concentration, and decreasing temperature
and pH [1]. The latter is an important factor in urate stoneformation
in patients with acidic urine. The serum level of
urate in man considered to be ‘normal’ varies among laboratories
and in publications, but a range of 3.5 mg/dL
(0.2 mmol/L) to 7.0 mg/dL (0.4 mmol/L) is often quoted.
Serum urate is usually 0.5-1 mg/dL (0.03-0.06 mmol/L)
lower in women compared with men. Serum urate levels in
men have increased gradually from 3.5 mg/dl (0.2 mmol/L)
in the 1920s to 6.0 mg/dL (0.35 mmol/L) in the 1970s [2].
However, no explanation for this observation has been
given, but it is probably related to changes in diet, e.g., increased
intake of fructose.
The serum urate level depends on dietary purines, the
degradation of endogenous purines, and the renal and intestinal
excretion of urate. The dominating factor contributing
to hyperuricaemia is under-excretion of urate [1].