Abstract
Acetylation of added (-)carnitine by heart mitochondira coupled to the oxidation of pyruvate in the presence of malonate was inhibited, apparently competitively, by long chain acyl(+)carnitines although the activity of carnitine acetyltransferase (EC 2.3.1.7) itself was not affected. Mitochondria have been found to possess a translocase system that allows the transport of carnitine and acylcarnitines by exchange diffusion, and interaction with this transport appears to be the cause of long chain acyl(+)carnitine inhibition. These c-nclusions are based on the following observations: (a) exposure of intact, but not of denatured or disrupted, mitochondria to [14-C]carnitine efflux was saturable at low lwvels of carnitine or acylcarnitines, showed temperature dependence, and was more rapid with acyl(-)carnitines than with acyl(+)carnitines--such stereospecificity was not noticeable with free carnitine; (c) long chain acyl-(+)carnitines inhibited the carnitine-carnitine exchange and higher concentrations of carnitine decreased this inhibition; (d) direct estimations showed the presence of endogenous (-)carnitine in mitochondria that effluxed by freezing and thawing of mitochondria; (e) the amount of total endogenous (-)carnitine present was not affected by prior exposure of mitochondria to (-)carnitine or acetyl(-)carnitine. These results indicate that the carnitine-dependent translocation of acyl groups across mitochondrial inner membrane involves the participation of a carnitine acylcarnitine translocase system.
Full text
PDF




Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Brdiczka D., Gerbitz K., Pette D. Localization and function of external and internal carnitine acetyltransferases in mitochondria of rat liver and pig kidney. Eur J Biochem. 1969 Dec;11(2):234–240. doi: 10.1111/j.1432-1033.1969.tb00765.x. [DOI] [PubMed] [Google Scholar]
- Brosnan J. T., Fritz I. B. The permeability of mitochondria to carnitine and acetylcarnitine. Biochem J. 1971 Dec;125(4):94P–95P. doi: 10.1042/bj1250094pb. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Brosnan J. T., Kopec B., Fritz I. B. The localization of carnitine palmitoyltransferase on the inner membrane of bovine liver mitochondria. J Biol Chem. 1973 Jun 10;248(11):4075–4082. [PubMed] [Google Scholar]
- Cederblad G., Lindstedt S. A method for the determination of carnitine in the picomole range. Clin Chim Acta. 1972 Mar;37:235–243. doi: 10.1016/0009-8981(72)90438-x. [DOI] [PubMed] [Google Scholar]
- Chase J. F., Tubbs P. K. Specific inhibition of mitochondrial fatty acid oxidation by 2-bromopalmitate and its coenzyme A and carnitine esters. Biochem J. 1972 Aug;129(1):55–65. doi: 10.1042/bj1290055. [DOI] [PMC free article] [PubMed] [Google Scholar]
- FRITZ I. B., SCHULTZ S. K., SRERE P. A. Properties of partially purified carnitine acetyltransferase. J Biol Chem. 1963 Jul;238:2509–2517. [PubMed] [Google Scholar]
- FRITZ I. B., YUE K. T. LONG-CHAIN CARNITINE ACYLTRANSFERASE AND THE ROLE OF ACYLCARNITINE DERIVATIVES IN THE CATALYTIC INCREASE OF FATTY ACID OXIDATION INDUCED BY CARNITINE. J Lipid Res. 1963 Jul;4:279–288. [PubMed] [Google Scholar]
- Fritz I. B., Marquis N. R. The role of acylcarnitine esters and carnitine palmityltransferase in the transport of fatty acyl groups across mitochondrial membranes. Proc Natl Acad Sci U S A. 1965 Oct;54(4):1226–1233. doi: 10.1073/pnas.54.4.1226. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Haddock B. A., Yates D. W., Garland P. B. The localization of some coenzyme A-dependent enzymes in rat liver mitochondria. Biochem J. 1970 Sep;119(3):565–573. doi: 10.1042/bj1190565. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hoppel C. L., Tomec R. J. Carnitine palmityltransferase. Location of two enzymatic activities in rat liver mitochondria. J Biol Chem. 1972 Feb 10;247(3):832–841. [PubMed] [Google Scholar]
- Levitsky D. O., Skulachev V. P. Carnitine: the carrier transporting fatty acyls into mitochondria by means of an electrochemical gradient of H + . Biochim Biophys Acta. 1972 Jul 12;275(1):33–50. doi: 10.1016/0005-2728(72)90022-9. [DOI] [PubMed] [Google Scholar]
- Norum K. R., Bremer J. The localization of acyl coenzyme A-carnitine acyltransferases in rat liver cells. J Biol Chem. 1967 Feb 10;242(3):407–411. [PubMed] [Google Scholar]
- Pande S. V., Blanchaer M. C. Reversible inhibition of mitochondrial adenosine diphosphate phosphorylation by long chain acyl coenzyme A esters. J Biol Chem. 1971 Jan 25;246(2):402–411. [PubMed] [Google Scholar]
- Pande S. V. On rate-controlling factors of long chain fatty acid oxidation. J Biol Chem. 1971 Sep 10;246(17):5384–5390. [PubMed] [Google Scholar]
- Tubbs P. K., Garland P. B. Membranes and fatty acid metabolism. Br Med Bull. 1968 May;24(2):158–164. doi: 10.1093/oxfordjournals.bmb.a070619. [DOI] [PubMed] [Google Scholar]
- West D. W., Chase J. F., Tubbs P. K. The separation and properties of two forms of carnitine palmitoyltransferase from ox liver mitochondria. Biochem Biophys Res Commun. 1971 Mar 5;42(5):912–918. doi: 10.1016/0006-291x(71)90517-1. [DOI] [PubMed] [Google Scholar]
- Yates D. W., Garland P. B. Carnitine palmitoyltransferase activities (EC 2.3.1.-) of rat liver mitochondria. Biochem J. 1970 Sep;119(3):547–552. doi: 10.1042/bj1190547. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zahlten R. N., Hochberg A. A., Stratman F. W., Lardy H. A. Pyruvate uptake in rat liver mitochondria: Transport or adsorption? FEBS Lett. 1972 Mar;21(1):11–13. doi: 10.1016/0014-5793(72)80150-9. [DOI] [PubMed] [Google Scholar]
- Ziegler H. J., Bruckner P., Binon F. O-acylation of dl-carnitine chloride. J Org Chem. 1967 Dec;32(12):3989–3991. doi: 10.1021/jo01287a057. [DOI] [PubMed] [Google Scholar]