RESUMO
The L-lactate/proton symport system of the red blood cell membrane was studied under conditions of alternative-substrate inhibition by glycolate. At constant pH of the medium glycolate caused competitive inhibition of L-lactate transport. In Lineweaver-Burk plots of 1/v against 1/[H], on the other hand, glycolate caused an uncompetitive inhibition. These observations indicate, that the monocarboxylate carrier exhibits ordered substrate binding, with the proton binding first.
Assuntos
Proteínas de Transporte/antagonistas & inibidores , Eritrócitos/metabolismo , Glicolatos/farmacologia , Lactatos/metabolismo , Humanos , Concentração de Íons de Hidrogênio , Cinética , Ácido Láctico , Matemática , Transportadores de Ácidos MonocarboxílicosRESUMO
Three parallel pathways of L-lactate transport across the membrane of human red blood cells can be discriminated: (a) by nonionic diffusion; (b) via the band 3 anion exchange protein; and (c) via a specific monocarboxylate carrier system. Influx of lactate via the latter system leads to alkalinization of the medium, suggesting lactate-proton symport. Kinetic analysis of initial lactate influx via the monocarboxylate carrier indicates a symport system with ordered binding of the two ligands, in the sense that a proton binds first to the translocator, followed by lactate binding to the protonated carrier. The influence of varying trans-pH under conditions of net (zero-trans) flux with constant cis-pH indicates that the monocarboxylate translocator should be considered as a mobile carrier, with the ligand-binding sites exposed alternatively to the outside and the inside of the membrane.
