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  • Title: Inhibition of mitochondrial carnitine acylcarnitine translocase by hypoglycaemia-inducing substances.
    Author: Beneking M, Oellerich M, Binder L, Choitz GF, Haeckel R.
    Journal: J Clin Chem Clin Biochem; 1990 May; 28(5):323-7. PubMed ID: 2116497.
    Abstract:
    The rate of mitochondrial carnitine-carnitine exchange mediated by carnitine acylcarnitine translocase was measured in the presence of the two hypoglycaemia-inducing drugs, 2-(3-methyl-cinnamyl-hydrazono)-propionate and 2-(3-phenylpropoxyimino)-butyric acid (BM 13.677). Both substances caused a concentration-dependent decrease in the rate of carnitine uptake in guinea pig liver mitochondria. Apparent initial influx rates were decreased by 75% and 80% at a concentration of 2 mmol/l 2-(3-methyl-cinnamyl-hydrazono)-propionate and 2-(3-phenylpropoxyimino)-butyric acid, respectively. Intraperitoneal injections of 212 mumol 2-(3-phenylpropoxyimino)-butyric acid or 21 mumol 2-(3-methyl-cinnamyl-hydrazono)-propionate per kg body weight caused a noticeable decrease in blood glucose concentration. A significant fall of the blood ketone body concentration was achieved with 2-(3-methyl-cinnamyl-hydrazono)-propionate or 2-(3-phenylpropoxyimino)-butyric acid, at dosages of 21 and 255 mumol/l, respectively. Furthermore there was a dose-dependent increase in the plasma free fatty acid concentration in the presence of 2-(3-methyl-cinnamyl-hydrazono)-propionate. This increase, however, was much less pronounced with 2-(3-phenylpropoxyimino)-butyric acid. Metabolic effects of 2-(3-methyl-cinnamyl-hydrazono)-propionate are consistent with an inhibition of long-chain fatty acid transport, whereas an additional mechanism of action has to be assumed for 2-(3-phenylpropoxyimino)-butyric acid.
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