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. 1980 Dec 15;192(3):959–962. doi: 10.1042/bj1920959

Evaluation of malonyl-CoA in the regulation of long-chain fatty acid oxidation in the liver. Evidence for an unidentified regulatory component of the system.

J A Ontko, M L Johns
PMCID: PMC1162425  PMID: 7236249

Abstract

Palmitate oxidation by liver mitochondria from fed and starved rats exhibited markedly different sensitivities to inhibition by malonyl-CoA. In the mitochondrial system from fed rats, 50% inhibition required 19 muM-malonyl-CoA, whereas the mitochondria from starved rats were by comparison refractory to malonyl-CoA. Inhibition by malonyl-CoA was completely reversed by increasing the molar ratio of fatty acid to albumin. Results indicate that the potential effectiveness of malonyl-CoA as an inhibitor of fatty acid oxidation in the liver is dependent on an unidentified regulatory component of the system. The functional activity of this component is modified by the nutritional state, and its site of action is at the mitochondrial level.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Cook G. A., King M. T., Veech R. L. Ketogenesis and malonyl coenzyme A content of isolated rat hepatocytes. J Biol Chem. 1978 Apr 25;253(8):2529–2531. [PubMed] [Google Scholar]
  2. Cook G. A., Otto D. A., Cornell N. W. Differential inhibition of ketogenesis by malonyl-CoA in mitochondria from fed and starved rats. Biochem J. 1980 Dec 15;192(3):955–958. doi: 10.1042/bj1920955. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Kondrup J., Grunnet N. The effect of acute and prolonged ethanol treatment on the contents of coenzyme A, carnitine and their derivatives in rat liver. Biochem J. 1973 Mar;132(3):373–379. doi: 10.1042/bj1320373. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. McGarry J. D., Foster D. W. In support of the roles of malonyl-CoA and carnitine acyltransferase I in the regulation of hepatic fatty acid oxidation and ketogenesis. J Biol Chem. 1979 Sep 10;254(17):8163–8168. [PubMed] [Google Scholar]
  5. McGarry J. D., Leatherman G. F., Foster D. W. Carnitine palmitoyltransferase I. The site of inhibition of hepatic fatty acid oxidation by malonyl-CoA. J Biol Chem. 1978 Jun 25;253(12):4128–4136. [PubMed] [Google Scholar]
  6. McGarry J. D., Mannaerts G. P., Foster D. W. A possible role for malonyl-CoA in the regulation of hepatic fatty acid oxidation and ketogenesis. J Clin Invest. 1977 Jul;60(1):265–270. doi: 10.1172/JCI108764. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. McGarry J. D., Mannaerts G. P., Foster D. W. Characteristics of fatty acid oxidation in rat liver homogenates and the inhibitory effect of malonyl-CoA. Biochim Biophys Acta. 1978 Sep 28;530(3):305–313. doi: 10.1016/0005-2760(78)90150-9. [DOI] [PubMed] [Google Scholar]
  8. McGarry J. D., Robles-Valdes C., Foster D. W. Role of carnitine in hepatic ketogenesis. Proc Natl Acad Sci U S A. 1975 Nov;72(11):4385–4388. doi: 10.1073/pnas.72.11.4385. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. McGarry J. D., Takabayashi Y., Foster D. W. The role of malonyl-coa in the coordination of fatty acid synthesis and oxidation in isolated rat hepatocytes. J Biol Chem. 1978 Nov 25;253(22):8294–8300. [PubMed] [Google Scholar]
  10. Otto D. A., Ontko J. A. Activation of mitochondrial fatty acid oxidation by calcium. Conversion to the energized state. J Biol Chem. 1978 Feb 10;253(3):789–799. [PubMed] [Google Scholar]
  11. Pande S. V. A mitochondrial carnitine acylcarnitine translocase system. Proc Natl Acad Sci U S A. 1975 Mar;72(3):883–887. doi: 10.1073/pnas.72.3.883. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Pande S. V., Parvin R. Carnitine-acylcarnitine translocase catalyzes an equilibrating unidirectional transport as well. J Biol Chem. 1980 Apr 10;255(7):2994–3001. [PubMed] [Google Scholar]
  13. Parvin R., Pande S. V. Enhancement of mitochondrial carnitine and carnitine acylcarnitine translocase-mediated transport of fatty acids into liver mitochondria under ketogenic conditions. J Biol Chem. 1979 Jun 25;254(12):5423–5429. [PubMed] [Google Scholar]
  14. Peters T., Jr, Peters J. C. The biosynthesis of rat serum albumin. VI. Intracellular transport of albumin and rates of albumin and liver protein synthesis in vivo under various physiological conditions. J Biol Chem. 1972 Jun 25;247(12):3858–3863. [PubMed] [Google Scholar]
  15. Ramsay R. R., Tubbs P. K. The mechanism of fatty acid uptake by heart mitochondria: an acylcarnitine-carnitine exchange. FEBS Lett. 1975 Jun 1;54(1):21–25. doi: 10.1016/0014-5793(75)81059-3. [DOI] [PubMed] [Google Scholar]
  16. Snoswell A. M., Koundakjian P. P. Relationships between carnitine and coenzyme A esters in tissues of normal and alloxan-diabetic sheep. Biochem J. 1972 Mar;127(1):133–141. doi: 10.1042/bj1270133. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. WILLIAMSON D. H., MELLANBY J., KREBS H. A. Enzymic determination of D(-)-beta-hydroxybutyric acid and acetoacetic acid in blood. Biochem J. 1962 Jan;82:90–96. doi: 10.1042/bj0820090. [DOI] [PMC free article] [PubMed] [Google Scholar]

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