Towards the physiological function of uric acid

Abstract

Uric acid, or more correctly (at physiological pH values), its monoanion urate, is traditionally considered to be a metabolically inert end-product of purine metabolism in man, without any physiological value. However, this ubiquitous compound has proven to be a selective antioxidant, capable especially of reaction with hydroxyl radicals and hypochlorous acid, itself being converted to innocuous products (allantoin, allantoate, glyoxylate, urea, oxalate). There is now evidence for such processes not only in vitro and in isolated organs, but also in the human lung in vivo. Urate may also serve as an oxidisable cosubstrate for the enzyme cyclooxygenase. As shown for the coronary system, a major site of production of urate is the microvascular endothelium, and there is generally a net release of urate from the human myocardium in vivo. In isolated organ preparations, urate protects against reperfusion damage induced by activated granulocytes, cells known to produce a variety of radicals and oxidants. Intriguingly, urate prevents oxidative inactivation of endothelial enzymes (cyclooxygenase, angiotensin converting enzyme) and preserves the ability of the endothelium to mediate vascular dilatation in the face of oxidative stress, suggesting a particular relationship between the site of urate formation and the need for a biologically potent radical scavenger and antioxidant.