0000000000255791
AUTHOR
Marcelline Tsoko
Reciprocal Enzymatic Interference of Carnitine Palmitoyltransferase I and Glycerol-3-Phosphate Acyltransferase in Purified Liver Mitochondria
(i) Highly purified mitochondrial fractions were practically devoid of microsomal contamination and of acyl-CoA ligase activity. (ii) In mitochondria, glycerol-3-phosphate acyltransferase (GPAT) activity was supported by two enzymes, the first being very active at low palmitoyl-CoA / albumin ratios and sensitive to external agents (external form), the second being detected only at higher palmitoyl-CoA / albumin ratios and insensitive to external agents (internal form). (iii) Carnitine palmitoyltransferase I (CPT I) activity was shown to inhibit external GPAT activity only. (iv) Glycerol-3-phosphate exerted an inhibitory effect on CPT I, even when GPAT was inactive. Reciprocal interaction of…
Fatty acid oxidation and related gene expression in heart depleted of carnitine by mildronate treatment in the rat.
The metabolic and genic effects induced by a 20-fold lowering of carnitine content in the heart were studied in mildronate-treated rats. In the perfused heart, the proportion of palmitate taken up then oxidized was 5-10% lower, while the triacylglycerol (TAG) formation was 100% greater than in controls. The treatment was shown to increase the maximal capacity of heart homogenates to oxidize palmitate, the mRNA level of carnitine palmitoyltransferase I (CPT-I) isoforms, the specific activity of CPT-I in subsarcolemmal mitochondria and the total carnitine content of isolated mitochondria. Concomitantly, the increased mRNA expression of lipoprotein lipase, fatty acid translocase and enzymes of…
Hypolipidaemic effects of fenofibrate are not altered by mildronate-mediated normalization of carnitine concentration in rat liver.
The five-fold higher carnitine content in the liver of fenofibrate-treated rats addresses the question about the possible role of this enhancement in the hypolipidaemic effect of the drug and the underlying mechanisms. When fenofibrate was administered with mildronate (a gamma-butyrobetaine hydroxylase inhibitor) in suitable amount, the content in carnitine was found to be normalized in liver. However, triglyceride contents of liver and serum were then at least as low as in rats treated by fenofibrate only. When carnitine concentration was lowered by mildronate to the third of the normal value, a marked increase in triglycerides occurred both in liver and serum, while the five-fold increase…
Enhancement of activities relative to fatty acid oxidation in the liver of rats depleted of l-carnitine by d-carnitine and a γ-butyrobetaine hydroxylase inhibitor
Abstract This study was designed to examine whether the depletion of l -carnitine may induce compensatory mechanisms allowing higher fatty acid oxidative activities in liver, particularly with regard to mitochondrial carnitine palmitoyltransferase I activity and peroxisomal fatty acid oxidation. Wistar rats received d -carnitine for 2 days and 3-(2,2,2-trimethylhydrazinium)propionate (mildronate), a non-competitive inhibitor of γ-butyrobetaine hydroxylase, for 10 days. They were starved for 20 hr before being sacrificed. A dramatic reduction in carnitine concentration was observed in heart, skeletal muscles and kidneys, and to a lesser extent, in liver. Triacylglycerol content was found to …
Effects of dietary treatment of rats with eicosapentaenoic acid or docosahexaenoic acid on hepatic lipid metabolism
(1) Effects of dietary treatment of male albino rats with eicosapentaenoic acid (EPA) or docosahexaenoic acid on hepatic mitochondrial lipid metabolism have been investigated. (2) Mitochondria isolated from rats given these treatments were shown to have increased ability to respire on acyl-CoA esters in the presence of malonate. This effect was expressed with most of the long-chain acyl-CoA esters used as substrates. When malonate in the incubations was replaced with malate, mitochondria from treated animals were found to exhibit diminished rates of respiration on polyunsaturated acyl-CoA esters, in particular linolenoyl-, eicosapentaenoyl- and docosahexaenoyl-CoA. This phenomenon could not…