BACKGROUND AND OBJECTIVES Cystinuria is a rare inherited renal stone disease. Mutations in the amino acid exchanger System b(0,+), the two subunits of which are encoded by SLC3A1 and SLC7A9, predominantly underlie this disease. The work analyzed the epidemiology of cystinuria and the influence of mutations in these two genes on disease severity in a United Kingdom cohort. DESIGN, SETTING, PAR...

Intracellular thiols like L-cystine and L-cystine play a critical role in the regulation of cellular processes. Here we show that Escherichia coli has two L-cystine transporters, the symporter YdjN and the ATP-binding cassette importer FliY-YecSC. These proteins import L-cystine, an oxidized product of L-cystine from the periplasm to the cytoplasm. The symporter YdjN, which is expected to be a ...

During treatment with oxidizing agents, the disulfide sulfur in wool appears to be changed to higher states of oxidation. The exist ence of oxidation derivatives of the disulfide compounds is indicated by the alkali-solubility determination, the lead acetate test, b y reduction with hydrochloric acid-potassium iodide solutions, and by cystine analyses. The intermediate oxidation derivatives of ...

Normal leucocyte lysosome-rich granular fractions exhibited counter-transport of cystine, confirming that cystine transport across the lysosomal membrane is carrier-mediated. The trans-activation of cystine transport was temperature-dependent but relatively independent of the external Na+ or K+ concentration in phosphate buffer. Counter-transport, measured as uptake of exogenous [3H]cystine, in...

Previous studies with cystinuric dogs and humans have demonstrated that the amount of cystine excreted in the urine is, in some cases, larger than the amount of cystine removed from the plasma by glomerular filtration. It was concluded that the kidney must secrete cystine into the renal tubule. The present studies indicate that renal glutathione turnover constitutes a mechanism of cystine secre...

Cystine and cysteine are important molecules for pathways such as redox signaling and regulation, and thus identifying cellular deficits upon deletion of the Saccharomyces cerevisiae cystine transporter Ers1p allows for a further understanding of cystine homeostasis. Previous complementation studies using the human ortholog suggest yeast Ers1p is a cystine transporter. Human CTNS encodes the pr...

It is well established that when cystine-depleted cystinotic cells are cultured in cystine-containing medium, they reaccumulate cystine within their lysosomes more rapidly than when cultured in cystine-free medium. This has been a puzzling result, since the lysosome membrane of cystinotic cells is impermeable to cystine. To probe the mechanism of cystine reaccumulation, we have measured reaccum...

Cystinotic fibroblasts contain approximately 100 times more cystine than do normal control fibroblasts. When cystinotic fibroblasts were placed in the presence of 30 mM cysteine-glutathione mixed disulfide (CSSG) for 24 hr, their cystine content increased about 3-fold. Similar treatment of normal fibroblasts and fibroblasts from patients heterozygous for cystinosis resulted in a 6- to 7-fold in...

Lysosomes containing large amounts of the amino acid, cystine, were obtained from transformed, cultured, human lymphoblasts which had been exposed to cystine dimethyl ester. Lysosomal cystine efflux was greatly enhanced by exogenous ATP in cell lines from normal individuals. Cystine efflux was unresponsive to ATP in lysosomes from individuals with the disorder, cystinosis. Efflux of cystine fro...