Voprosy meditsinskoi khimii (ISSN 0042-8809)

Regulation of carnitine-dependent metabolism of fatty acids in the rat myocardium using 3-(2,2,2-trimethylhydrazinium) propionate

   
Shutenko Zh.V., Simkhovich B.Z., Meirena D.V., Kalvin'sh I.Ia., Lukevits E.Ia.
PubMed Id: 2741413
Year: 1989 vol: 35  issue:2  pages: 59-64
Abstract: 3-(2,2,2-Trimethyl hydrazinium) propionate (THP), possessing a cardioprotective effect, is a noncompetitive inhibitor of butyrobetaine hydroxylase and inhibits fatty acid oxidation. The effect of THP, detected during the drug medicinal application, was related to inhibition of carnitine biosynthesis. THP exhibited the inhibitory action on carnitine acetyl transferase contributing to an increase in acetyl-CoA availability for intramitochondrial metabolic pathways. The drug prevented L-carnitine induced stimulation of U-14C-palmitic acid oxidation in vitro. During administration as well as after addition into incubation medium THP did not show any significant effects on 1-14C-palmitoyl-L-carnitine oxidation but decreased the exogenous L-carnitine induced oxidation of the substrate in vitro. The drug did not affect the activity of carnitine palmitoyl transferase I. Action of THP on the carnitine-dependent oxidation of fatty acids might be related to the drug inhibitory effect on activities either of carnitine acyl transferase II or carnitine acylcarnitine translocase. The data obtained suggest that THP carried out the following functions: 1) inhibition of carnitine biosynthesis, 2) direct inhibition of carnitine dependent transport of fatty acids in mitochondria, 3) inhibition of carnitine acetyl transferase. Inhibition of carnitine dependent oxidation of fatty acids at the step of their activation was the drug integral effect.
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Reference: Shutenko Zh.V., Simkhovich B.Z., Meirena D.V., Kalvin'sh I.Ia., Lukevits E.Ia., Regulation of carnitine-dependent metabolism of fatty acids in the rat myocardium using 3-(2,2,2-trimethylhydrazinium) propionate, Voprosy meditsinskoi khimii, 1989, vol: 35(2), 59-64.
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