BIOGENESIS OF L-GLYCERIC ACIDURIA, OXALOSIS AND RENAL INJURY IN RATS SIMULATING TYPE-II PRIMARY HYPEROXALURIA

Tracer experiments in rats mimicking type II primary hyperoxaluria, wi th an expanded intracellular pool of hydroxypyruvate, showed that the excess formation of oxalate did not originate from its immediate precu rsor glyoxylate. In these animals, the hepatic and kidney activities o f oxalate synthesising enzymes such as lactate dehydrogenase and glyco late oxidase were normal, but tissue lipid peroxidation was significan tly higher. In vitro experiments established that in a mild alkaline s olution, hydroxypyruvate underwent auto-oxidation to form oxalate and H2O2 and also inhibited lactate dehydrogenase and glycolate oxidase fr om oxidising glyoxylate to oxalate. On the basis of the experimental e vidence, we suggest that in type II primary hyperoxaluria, the accumul ating hydroxypyruvate could reduce the intracellular pool of glyoxylat e and on ageing, give rise to excess oxalate and H2O2, to cause oxalos is in the former and free radical mediated-cell injuries in the latter . (C) 1997 Elsevier Science B.V.