In vitro studies on the metabolism of hexadecanedioic acid and its mono-l-carnitine- ester
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Add time:09/03/2019 Source:sciencedirect.com
1.1. A method for the synthesis of the mono-L-carnitine ester of hexadecanedioic acid (hexadecanedioylcarnitine) is described. A thin-layer chromatography system for the separation of long-chain monocarboxylic and long-chain dicarboxylic acylcarnitines was developed.2.2. Hexadecanedioic acid can be activated by rat liver mitochondria in the presence of CoA, ATP, and Mg2+. Since Triton X-Ioo does not increase the activation capacity, the enzyme(s) activating long-chain dicarboxylic acids seems to be localized outside the inner mitochondrial compartment.3.3. Hexadecanedioylcarnitine is substrate for a solubilized preparation of hexadecanoyl-CoA:carnitineO-hexadecanoyltransferase (EC 2.3.1.-), but the reaction rate is only about 1/10 of that with palmitylcarnitine. Accordingly, mitochondrial CoA can be acylated by hexadecanoylcarnitine, but much slower than by palmitylcarnitine.4.4. Hexadecanedioylcarnitine competes with palmitylcarnitine in the reaction catalyzed by the enzyme.5.5. In fasted, ketotic streptozotocin-diabetic, and clofibrate-fed rats the carnitine acyltransferase activity was significantly increased. The relative increases were about the same whether hexadecanedioylcarnitine or palmitylcarnitine were used as substrates.6.6. The observations under points 4 and 5 indicate that the same enzyme (hexadecanoyl-CoA:carnitineO-hexadecanoyltransferase, EC 2.3.1.-) may transport activated hexadecanedioic as well as palmitic acid across the inner mitochondrial membrane.7.7. The O2 uptake of rat heart and liver mitochondria with hexadecanedioylcarnitine as substrate was very low and transitory. Hexadecanedioylcarnitine did not inhibit the oxidation of palmitylcarnitine.8.8. The present in vitro studies demonstrate a possible mechanism for the degradation of long-chain dicarboxylic acids, viz. activation by CoA and transportation into the inner mitochondrial compartment as carnitine esters followed by β-oxidation.
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