The synthesis of oxalate from hydroxypyruvate by isolated perfused rat liver the mechanism of hyperoxaluria in L-lyceric aciduria

Abstract

Hydroxypyruvate and glycolate inhibited the oxidation of [U- 14C]glyoxylate to [ 14C]oxalate in isolated perfused rat liver, but stimulated total oxalate and glycolate synthesis. [ 14C]Oxalate synthesis from [ 14C]glycine similarly inhibited by hydroxypyruvate, but conversion of [ 14C 1]glycolate to [ 4C]oxalate was increased three-fold. Pyruvate had no effect on the synthesis of [ 14C]oxalate or total oxalate. The inhibition studies suggest that hydroxypyruvate is a precursor of glycolate and oxalate and that the conversion of glycolate to oxalate does not involve free glyoxylate as an intermediate. [ 14C 3]Hydroxypyruvate, but not [ 14C 1]hydroxypyruvate, was oxidized to [ 14C]oxalate in isolated perfused rat liver. Isotope dilution studies indicate the major pathway involves the decarboxylation of hydroxypyruvate forming glycolaldehyde which is subsequently oxidized to oxalate via glycolate. The oxidation of serine to oxalate appears to proceed predominantly via hydroxypyruvate rather than glycine or ethanolamine. The hyperoxaluria of L-glyceric aciduria, primary hyperoxaluria type II, is induced by the oxidation of the hydroxypyruvate, which accumulates because of the deficiency of D-glyceric dehydrogenase, to oxalate.