Urate oxidation by cupric ion (Cu

Uric acid or urate, a compound of extremely limited solubility produced in vivo by degradation of purines from nucleic acids or other endogenous and exogenous sources has long been considered a metabolic “enfant terrible” of man. Possessing a vestigial uricotelic apparatus but lacking the copper-containing enzyme uricase which oxidizes urate to water-soluble compounds, man teters on the brink of urico-disaster. Although elaborate control mechanisms exist to prevent flooding by urate, when these systems fail for genetic or other reasons body urate pools increase and there is danger of precipitation in soft tissues, cartilage (tophi) and urine (stones). While the major portion (60-70%) of the urate disappearing from the urate pool is excreted as such in urine, the remainder may be converted to CO,, allantoin, allantoic acid, urea, and NH, by bacteria of the gastrointestinal tract [ 1 J . In addition oxygen uptake studies have revealed that urate may be oxidized by Cu++ above pH 10 and by the cytochrome oxidase system (Cu++?) at pH 7.9 [2]. Hemoproteins in the presence of peroxide causes breakdown of urate to allantoin, CO, and alloxanic acid [3]. We are reporting in vitro urate oxidation mediated solely by Cu++ at pH 6.0-8.2. In fig. 1 the fall in absorption of a urate solution incubated with Cu++ (urate/Cu++ ratio 1:4) is shown. Cu++ also alters the shape of the urate absorption spectrum drastically, obliterating the second maximum at 237 rnp. H,S