Y+- and L-system amino acid transport in normal and chronic lymphocytic leukemia lymphocytes: photoinhibition by fluoronitrophenylazide.
Three major pathways mediate amino acid transport into mammalian cells: the A-system and the ASC-system, which require a sodium gradient across the plasma membrane, and the L-system, which has no requirement for a sodium gradient. We have found that the lymphocytes from patients with B-cell chronic lymphocytic leukemia (CLL) have a marked reduction in the L-system of amino acid transport when compared to normal human B-lymphocytes from blood or tonsils. Transport by the A- and ASC-systems was not decreased in CLL B-lymphocytes. Because of the specific defect of the sodium-independent L-system amino acid transport in CLL cells, we have examined the activity of another sodium-independent transport system, the Y+-system, in human lymphocytes. The Y+-system favors the transport of dibasic, cationic amino acids such as lysine, ornithine, and arginine, which carry a positively charged group on their side chains. Our studies indicate that there is a large nonsaturable component of amino acid transport by the Y+-system in human lymphocytes. Using a multicomponent mathematical analysis, we have determined that the saturable component of Y+-transport is similar in T- (thymus-derived) and B- (bone-marrow-derived) lymphocytes and is unimpaired in CLL B-lymphocytes. Further, fluoronitrophenylazide, which was thought to be a specific inhibitor of the Y+-system when photoactivated, also inhibits A-, and L-system transport in CLL, T-, and B-lymphocytes.
D000596:Amino Acids / Q000378:metabolism*; D001386:Azides / Q000494:pharmacology*; D001402:B-Lymphocytes / Q000378:metabolism*; D001692:Biological Transport / Q000187:drug effects; D002470:Cell Survival; D006801:Humans; D007700:Kinetics; D007945:Leukemia, Lymphoid / Q000378:metabolism*; D008214:Lymphocytes / Q000187:drug effects; D008239:Lysine / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism*
D000596:Amino Acids; D001386:Azides; C007753:4-fluoro-3-nitrophenyl azide; D008239:Lysine