The Effects of Temperature and Some Inhibitors an the Carnitine Exchange System of Heart Mitochondria

Abstract

11-Trimethylamino-undecanoyl-L-carnitine (Ki = 56 .mu.M) and 6-trimethylaminohexanoyl-L-carnitine (Ki = 1.3 .mu.M) are competitive inhibitors of the ox heart mitochondrial carnitine exchange system. The latter is itself a poor substrate, with a V [enzyme reaction velocity] about 0.7% of that for carnitine. These compounds have been used as stop inhibitors in a study of the effect of temperature on the carnitine exchange. The carnitineout .tautm. carnitinein exchange has a temperature coefficient (Q10) of 8.5 and an activation energy of 176 kJ/mol which is constant from 0.degree.-18.degree. C. The Km for L-carnitine (5.3 mM) is also constant over this temperature range. The slow efflux (leak) of mitochondrial L-[14C]carnitine in the absence of external substrate has a similar temperature dependence and is also inhibited by 11-trimethylamino-undecanoyl-L-carnitine. It is probably mediated by the same system as the very much faster exchange with external carnitine.