Regulation of carnitine binding to plasma membranes by an ATP-dependent mechanism

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 KD of 20.7 +/- 3.5 microM. 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 microM. 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.