Choline transport into rat liver mitochondria. Characterization and kinetics of a specific transporter.
Rat liver mitochondria possess a specific choline transporter in the inner membrane. The transporter shows saturable kinetics at high membrane potential with a Km of 220 microM and a Vmax of 0.4 nmol/mg of protein/min at pH 7.0 and 25 degrees C. At physiological concentrations of choline, the rate of choline uptake by the transporter shows a linear dependence on membrane potential; uptake is distinct from the nonspecific cation diffusion process. Hemicholinium-3, hemicholinium-15, quinine, and quinidine, all analogues of choline, are high affinity competitive inhibitors of choline transport with Ki values of 17, 55, 15, and 127 microM, respectively. The choline transporter is distinct from other known mitochondrial transporters. Rat heart mitochondria do not appear to possess a choline transporter. Evidence suggests that the transporter is an electrophoretic uniporter. Analogue studies have shown that the hydroxyl and the quaternary ammonium groups of choline are necessary for binding to the transporter. A comparison of molecular models of choline and the high affinity inhibitors has provided evidence for the preferred conformation of choline for binding to the transporter. The presence of a choline transporter in the mitochondrial inner membrane provides a potential site for control of choline oxidation and hence supply of endogenous betaine.
Porter
R K
RK
Department of Biochemistry, Trinity College Dublin, Ireland.
Scott
J M
JM
Brand
M D
MD
D000818:Animals; D001692:Biological Transport; D002794:Choline / Q000031:analogs & derivatives / Q000378:metabolism*; D002855:Chromatography, Thin Layer; D007425:Intracellular Membranes / Q000502:physiology; D007700:Kinetics; D008564:Membrane Potentials; D008929:Mitochondria, Heart / Q000378:metabolism; D008930:Mitochondria, Liver / Q000378:metabolism*; D008933:Mitochondrial Swelling; D008958:Models, Molecular; D051381:Rats
D002794:Choline