Regulation of Carnitine Binding to Plasma Membranes by an ATP-Dependent Mechanism

Abstract

This is the first demonstration of L-carnitine binding to plasma membranes. Plasma membranes derived from S49 lymphoma cells bound 40.6 ± 5.7 pmol carnitine / mg membrane protein under basal conditions whereas addition of ATP in the presence of magnesium ions increased the number of carnitine binding sites to 557 ± 82 pmol / mg membrane protein, i.e., a 10-fold increase. Kinetic and equilibrium binding data indicated heterogeneity of carnitine binding sites. ATP modulated carnitine binding sites through a single class of sites at a KDof 20.7 ± 3.5 μM. The ATP effect seemed mediated by a protein tyrosine kinase as judged from the observed noncompetive inhibition of carnitine binding induced by genistein with a Ki= 65 ± 11 μM. Active cellular uptake of L-carnitine in S49 lymphoma cells was similarly reduced from 580 ± 35 to 421 ± 39 pmol / mg protein/h by genistein.