Arginine transport through system y(+)L in cultured human fibroblasts: normal phenotype of cells from LPI subjects

In lysinuric protein intolerance (LPI), impaired transport of cationic amin o acids in kidney and intestine is due to mutations of the SLC7A7 gene. To assess the functional consequences of the LPI defect in nonepithelial cells , we have characterized cationic amino acid (CAA) transport in human fibrob lasts obtained from LPI patients and a normal subject. In both cell types t he bidirectional fluxes of arginine are due to the additive contributions o f two Na+-independent, transstimulated transport systems. One of these mech anisms, inhibited by N-ethylmaleimide (NEM) and sensitive to the membrane p otential, is identifiable with system y(+). The NEM- and potential-insensit ive component, suppressed by L-leucine only in the presence of Na+, is most ly due to the activity of system y(+)L. The inward and outward activities o f the two systems are comparable in control and LPI fibroblasts. Both cell types express SLC7A1 (CAT1) and SLC7A2 (CAT2B and CAT2A) as well as SLC7A6 (y+LAT2) and SLC7A7 (y+LAT1). We conclude that LPI fibroblasts exhibit norm al CAA transport through system y(+)L, probably referable to the activity o f SLC7A6/y+LAT2.