Quantitative Aspects of Ascorbic Acid Metabolism in Man.

Ascorbic acid is catabolized to yield oxalate from carbon atoms 1 and 2 (1, 2) and carbon dioxide from carbon atom 1 in man as well as in other species (3-5). It has also been shown that n-glucuronolactone is converted to ascorbic acid in the human 63. The present studies were designed to determine the n-ascorbic acid metabolic pool size and turnover rate, the fraction of the urinary oxalate which arises from ascorbic acid, and the fractions of the total ascorbic acid turnover which give rise to urinary oxalate and urinary ascorbic acid, respectively. We used L-ascorbic acid-l-% and hence did not study the incorporation of the isotope into respiratory CO2 because of the extensive dilution of the isotope by CO2 arising from other metabolic pathways. The importance of ascorbic acid metabolism other than by renal excretion or oxalate formation was evaluated, and our mathematical analysis also takes account of ascorbic acid arising from sources other than the prescribed dietary intake. Oxalate is metabolically inert in animals and man (7-9), and our results enable us to compare the order of magnitude of the oxalate metabolic pool and its turnover rate with the corresponding parameters for ascorbic acid. The proportion of the urinary oxalate which was derived from glycine, which is another major precursor of urinary oxalate (7, 10, II), was also determined in the same subject. The measurement of a metabolic pool size and turnover rate by isotope dilution analysis involves sampling the metabolic pool. The ascorbic acid metabolic pool cannot be sampled directly in the human, and although the plasma ascorbic acid is presumably in equilibrium with that in the metabolic pool, the plasma ascorbic acid concentration is too low to permit the isolation of sufficient amounts of a derivative for mass spectrometric analysis. The urinary ascorbic acid is separated from the plasma by glomerular filtration and therefore samples the plasma ascorbic acid, and hence the ascorbic acid metabolic pool. Our chemical isolation procedure does not, however, distinguish between L-ascorbic acid, dehydro-n-ascorbic acid, and 2,3diketo-n-gulonic acid which are present in urine. The use of the uncombined urinary glycine as a sample of the glycine metabolic pool which gives rise to oxalate has been discussed elsewhere w.