The pathogenesis of cystinuria. II. Polarographic studies of the metabolism of sulfur-containing amino-acids.

The preceding paper (1) in this series describes some paper chromatographic and microbiological analyses of plasma and urine during acute experiments in which loading doses of cystine, cysteine, and methionine were given by mouth to normal and cystinuric subjects. Cysteine alone caused large rises in plasma cystine levels and urine outputs in both normal and cystinuric subjects. In all cases, urine output varied directly with plasma cystine levels, but in the cystinuric subjects the urine output was very much greater for any given plasma level than in the normal subject. The results were taken as strong evidence in favour of the renal theory of cystinuria, namely that the high cystine output of a cystinuric patient is due not to an innate inability to metabolize cystine or other sulphur-containing amino-acids but to a "low renal threshold" for cystine, presumably from defective tubular reabsorption. The methods of analysis used though highly specific qualitatively were not, however, considered sufficiently accurate quantitatively to enable renal clearances to be calculated. In this paper we have repeated in greater numbers experiments of the type described in the preceding paper (1) using an almost identical procedure for timing and collecting samples of plasma and urine. The cystine determinations, however, were done exclusively by polarography. This method, depending upon entirely different principles, is likely to be specific in the circumstances. There is no convincing evidence for the presence in these fluids (after deproteinization when necessary) of appreciable quantities of other substances which might interfere with the analysis owing to their containing .disulphide (-S-S-) or thiol