The Biosynthesis and Turnover of Oxalate

Oxalate is a normal constituent of human urine. Since oxalate is found in many foods it has frequently been assumed that urinary oxalate is largely, if not entirely, of dietary origin. However, animal studies have shown that oxalate may arise endogenously, and glycine, glyoxylic acid, glycolic acid (3-5) and ascorbic acid (6, 7) have been shown to be precursors of urinary or tissue oxalate under various circumstances. The origin of urinary oxalate has long been an important physiological problem because of the high incidence of calcium oxalate urolithiasis in many parts of the world. Recently, interest in the biosynthesis of oxalate in man has been greatly stimulated by recognition of the syndrome of primary hyperoxaluria and oxalosis, a disorder in which excessive production of oxalate occurs and leads to deposition of calcium oxalate crystals in renal parenchyma and extrarenal tissues. Ascorbic acid has previously been shown to be a precursor of some urinary oxalate of normal man (6, 8). In this paper glycine is shown to be a major precursor of urinary oxalate of normal and hyperoxaluric subjects. In one subject with primary hyperoxaluria, glycine incorporation into urinary oxalate was excessive, whereas in another subject with an inconstant hyperoxaluria, glycine incorporation was not abnormal. Measurements of the miscible pool of oxalate and of the rate of its turnover have been made by conventional isotopic dilution techniques, and a gross expansion of the miscible pool of oxalate demonstrated in a hyperoxaluric subject.