Inhibition of mitochondrial carnitine acylcarnitine translocase-mediated uptake of carnitine by 2-(3-methyl-cinnamyl-hydrazono)-propionate. Hydrazonopropionic acids, a new class of hypoglycaemic substances, VI.
The rate of mitochondrial carnitine-carnitine exchange mediated by carnitine acylcarnitine translocase was measured by following the uptake of L-[methyl-14C]carnitine. It was demonstrated that the hypoglycaemic compound 2-(3-methyl-cinnamyl-hydrazono)-propionate causes a concentration-dependent decrease in the rate of the translocase-mediated transport of carnitine in guinea pig liver mitochondria. Apparent initial influx rates were decreased by 20% at 0.3 mmol/1 2-(3-methyl-cinnamyl-hydrazono)-propionate, 38% at 0.5 mmol/l, and 75% at 2.0 mmol/l of this compound. This finding may explain the previously observed inhibitory effects of this substance on long-chain fatty acid oxidation, ketone body production and gluconeogenesis.
D000818:Animals; D002331:Carnitine / Q000378:metabolism* / Q000493:pharmacokinetics; D002333:Carnitine Acyltransferases; D002934:Cinnamates / Q000494:pharmacology*; D006168:Guinea Pigs; D006834:Hydrazines / Q000494:pharmacology*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D066298:In Vitro Techniques; D008930:Mitochondria, Liver / Q000201:enzymology*; D011422:Propionates / Q000494:pharmacology*; D014166:Transferases / Q000037:antagonists & inhibitors*
D002934:Cinnamates; D006834:Hydrazines; D007004:Hypoglycemic Agents; D011422:Propionates; C039804:BM 42304; D014166:Transferases; D002333:Carnitine Acyltransferases; D002331:Carnitine