Studies on the amino acid content of physiological fluids have usually been carried out under conditions that would permit any cysteine present to be oxidized to cystine prior to analysis. Consequently, little quantitative information has been obtained concerning the relative amounts of the -SH and the -S-S-forms of the amino acid in plasma. To know whether both forms are present is of particular importance in the study of excretion of amino acids by the kidney. Cystine is an amino acid which appears in abnormal quantities in the urine in several pathological conditions (1). Failure of tubular reabsorption has usually been invoked to explain this fact (2), an explanation which tacitly assumes that it is cystine (the -S-S-form) not cysteine (the -SH form) that is circulating in the blood and is cleared by the kidney. If cysteine were to be the predominant form normally circulating, oxidation to cystine in the kidney would be required in order to account for the excretion of the disulfide in the urine.Fujita and Numata (3) and Smith and Tuller (4) have reported the presence of cysteine in blood. Another observation which could bear on the subject is that of Brand, Cahill and Harris (5) who showed that the amount of cystine in the urine of a cystinuric subject rose after feeding cysteine and methionine, but not after the ingestion of cystine, the sulfur of which appeared almost exclusively as urinary sulfate.With these thoughts in view, a method has been developed to determine cysteine and cystine individually in the same sample of plasma. The method is based upon the fact that iodoacetate reacts rapidly with cysteine to convert it quantitatively to the stable S-carboxymethyl derivative, which can be determined chromatographically (6, 7). In the system of elution described (7,8) for
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