Palmityl Carnitine

There is abundant evidence indicating that a natural hydrophobic inhibitor of acetyl-CoA carboxylase is present in crude enzyme extracts of liver and adipose tissue [128,129,182,192,236-238]. The activating effect of (+)-palmityl carnitine on fatty acid synthesis in crude liver extracts and on impure acetyl-CoA carboxylase preparations has tentatively been ascribed to the displacement of hydrophobic inhibitors such as fatty acids or fatty acyl-CoA derivatives [129,182,192,236-238]. Inhibition of rat liver acetyl-CoA carboxylase by added palmityl-CoA can be reversed in part by (+)-palmityl carnitine [236], but not by citrate. This activating effect does not appear to be specific with respect to (+)-palmityl carnitine in that cetyl trimethylammonium ion is also effective [192]. Furthermore, impure preparations of acetyl-CoA carboxylase from adipose tissue or rat liver are markedly activated by serum albumin [123,129,238] or extensive dilution of the enzyme preparation prior to assay [129,182]. On the other hand, none of these agents [(+)-palmityl carnitine, serum albumin, or dilution], which activate the impure carboxylase, have an activating effect on the homogeneous acetyl-CoA carboxylases from adipose tissue or liver [129,182, 239]. It is evident that an inhibitory substance, apparently hydrophobic in nature, is removed either by purification of the enzyme or by the agents or treatments mentioned above. 

The initial formation of palmitylcarnitine occurs external to the membrane barrier to palmityl-CoA (reaction 1). Once transport has been effected, the palmitylcarnitine is reconverted to the coenz3nne A ester (reaction 2). The reaction catalyzed by palmitylcarnitine transferase is an equilibrium reaction so that under normal circumstances if oxidation is taking place the conversion of extra mitochondrial palmityl-CoA to palmityl carnitine does not become rate limiting for fatty acid oxidation. However, the situation during development is quite different and the generation of palmitylcarnitine external to the mitochondrial membrane barrier may impose constraints on fatty acid oxidation. 

Total CoA was estimated by the CoA-dependent incorporation of radioactive carnitine into palmityl carnitine (5) or by a recycling phosphotransacetylase method (cf. 2). 

These findings are consistent with impaired fatty-acid oxidation reduced mitochondrial entry of long-chain acylcarnitine esters due to inhibition of the transport protein (carnitine palmityl transferase 1) and failure of the respiratory chain at complex II. Another previously reported abnormality of the respiratory chain in propofol-infusion syndrome is a reduction in cytochrome C oxidase activity, with reduced complex IV activity and a reduced cytochrome oxidase ratio of 0.004. Propofol can also impair the mitochondrial electron transport system in isolated heart preparations. 

Bank WJ, DiMauro S, Bonilla E, Capuzzi DM, Rowland LP. A disorder of muscle lipid metabolism and myoglobinuria. Absence of carnitine palmityl transferase. N Engl J Med. 1975 292(9) 443-9. PubMed PMID 123038, Epub 1975/02/27. eng. 

Fig. 2. Comparison of palmityl-CoA plus carnitine oxidation by isolated fetal and calf heart mitochondria.

Fig. 5. Oxidation of palmityl-CoA plus carnitine by rat heart homogenates. Activity is expressed as nanoatoms oxygen utili7.ed/m.in/mg protein (Warshaw, 1972).

Carnitine in intermediary metabolism. The biosynthesis of palmityl-camitine by cell subfractions. J. biol. Chem. 238, 2774 (1963). 

A mixture of palmitic acid and SOCI2 stirred 3hrs. at 80°, then a soln. of dl-carnitine chloride in trichloracetic acid added at 40°, stirred and heated 3 hrs. at 80°, and poured into dry ether -> palmityl dl-carnitine chloride. Y 90%. F. e. and methods s. H. J. Ziegler, P. Bruckner, and F. Binon, J. Org. Chem. 32, 3989 (1967). 

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