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Abstract
Cellular accumulation of L-cystine in rat kidney cortex in vivo has been studied using L-[35S]cystine. The L-[35S]cystine radioactivity in plasma decreases to less than 10% of the initially calculated value by 15 min. Four 35S-containing intracellular products of L-cystine metabolism were identified including cystine, cysteine, reduced glutathione, and an as yet unidentified compound. The latter is probably taurine, cysteinesulphinate, or cysteic acid. Cellular accumulation of these products was found to be more rapid in vivo than in vitro. Cellular accumulation of the products of L-cystine metabolism was found to be essentially unchanged in the presence of ureter ligation. Unlabeled L-lysine administered simultaneously with L-[35S]cystine, in both the presence and absence or ureter ligation, enhanced the cellular accumulation of intracellular metabolic products of L-[35S]cystine. Simultaneous 35S cellular accumulation and L-cystine clearance studies were performed both in the presence and absence of L-lysine. L-Lysine enhanced cellular accumulation of 35S-products despite an accompanying increase in L-cystine clearance. The results are interpreted as evidence for a dissociation between cellular accumulation and transepithelial transport. This evidence for independent luminal transport and peritubular cellular accumulation could explain the apparent paradox in the disease cystinuria where there appears to be a luminal transport defect for L-cystine, but no defect for cellular accumulation of L-cystine metabolic products in vitro.
Authors
Warren E. Greth, Samuel O. Their, Stanton Segal
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ISSN: 0021-9738 (print), 1558-8238 (online)