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. 1977 Apr;74(4):1497–1501. doi: 10.1073/pnas.74.4.1497

Mechanism for acute control of fatty acid synthesis by glucagon and 3':5'-cyclic AMP in the liver cell.

P A Watkins, D M Tarlow, M D Lane
PMCID: PMC430816  PMID: 193102

Abstract

Labeling experiments with chicken liver cell monolayers and suspensions show that glucagon and N6, O2-dibutyryladenosine 3':5'-cyclic monophosphate (dibutyryl cyclic AMP) block fatty acid synthesis from acetate without appreciably affecting cholesterogenesis from acetate or acylglyceride synthesis from palmitate. Neither acetyl-CoA carboxylase [acetyl-CoA:carbon-dioxide ligase (ADP-forming), EC 6.4.1.2] activity assayed in the presence of citrate nor fatty acid synthetase activity is decreased in extracts of cells treated with glucagon. However, the cytoplasmic concentration of citrate, a required allosteric activator of acetyl-CoA carboxylase, is depressed more than 90% by glucagon or dibutyrl cyclic AMP. Pyruvate or lactate largely prevents the inhibitory action of these effectors on fatty acid synthesis by causing a large increase in cytoplasmic citrate level. Thus, it appears that glucagon, acting via cyclic AMP, inhibits fatty acid synthesis by blocking the formation of citrate, an essential activator of acetyl-CoA carboxylase.

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Selected References

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

  1. Allred J. B., Roehrig K. L. Inhibition of hepatic lipogenesis by cyclic-3',5'-nucleotide monophosphates. Biochem Biophys Res Commun. 1972 Feb 16;46(3):1135–1139. doi: 10.1016/s0006-291x(72)80092-5. [DOI] [PubMed] [Google Scholar]
  2. Bennett V., Cuatrecasas P. Mechanism of activation of adenylate cyclase by Vibrio cholerae enterotoxin. J Membr Biol. 1975 Jun 3;22(1):29–52. doi: 10.1007/BF01868162. [DOI] [PubMed] [Google Scholar]
  3. Bricker L. A., Levey G. S. Evidence for regulatin of cholesterol and fatty acid synthesis in liver by cyclic adenosine 3',5'-monophosphate. J Biol Chem. 1972 Aug 10;247(15):4914–4915. [PubMed] [Google Scholar]
  4. Carlson C. A., Kim K. H. Differential effects of metabolites on the active and inactive forms of hepatic acetyl CoA carboxylase. Arch Biochem Biophys. 1974 Oct;164(2):490–501. doi: 10.1016/0003-9861(74)90059-9. [DOI] [PubMed] [Google Scholar]
  5. Carlson C. A., Kim K. H. Regulation of hepatic acetyl coenzyme A carboxylase by phosphorylation and dephosphorylation. Arch Biochem Biophys. 1974 Oct;164(2):478–489. doi: 10.1016/0003-9861(74)90058-7. [DOI] [PubMed] [Google Scholar]
  6. Carlson C. A., Kim K. H. Regulation of hepatic acetyl coenzyme A carboxylase by phosphorylation and dephosphorylation. J Biol Chem. 1973 Jan 10;248(1):378–380. [PubMed] [Google Scholar]
  7. Chang H. C., Seidman I., Teebor G., Lane M. D. Liver acetyl CoA carboxylase and fatty acid synthetase: relative activities in the normal state and in hereditary obesity. Biochem Biophys Res Commun. 1967 Sep 7;28(5):682–686. doi: 10.1016/0006-291x(67)90369-5. [DOI] [PubMed] [Google Scholar]
  8. Exton J. H., Robison G. A., Sutherland E. W., Park C. R. Studies on the role of adenosine 3',5'-monophosphate in the hepatic actions of glucagon and catecholamines. J Biol Chem. 1971 Oct 25;246(20):6166–6177. [PubMed] [Google Scholar]
  9. Goodridge A. G. Regulation of fatty acid synthesis in isolated hepatocytes prepared from the livers of neonatal chicks. J Biol Chem. 1973 Mar 25;248(6):1924–1931. [PubMed] [Google Scholar]
  10. Gregolin C., Ryder E., Kleinschmidt A. K., Warner R. C., Lane M. D. Molecular characteristics of liver acetyl CoA carboxylase. Proc Natl Acad Sci U S A. 1966 Jul;56(1):148–155. doi: 10.1073/pnas.56.1.148. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hoek J. B., Tager J. M. The oxidoreduction state of free NAD(P) and mass-action ratio of total nicotinamide nucleotides in isolated rat-liver mitochondria. Biochim Biophys Acta. 1973 Nov 22;325(2):197–212. doi: 10.1016/0005-2728(73)90096-0. [DOI] [PubMed] [Google Scholar]
  12. Kleinschmidt A. K., Moss J., Lane D. M. Acetyl coenzyme A carboxylase: filamentous nature of the animal enzymes. Science. 1969 Dec 5;166(3910):1276–1278. doi: 10.1126/science.166.3910.1276. [DOI] [PubMed] [Google Scholar]
  13. Moss J., Lane M. D. Acetyl coenzyme A carboxylase. 3. Further studies on the relation of catalytic activity to polymeric state. J Biol Chem. 1972 Aug 25;247(16):4944–4951. [PubMed] [Google Scholar]
  14. Moss J., Yamagishi M., Kleinschmidt A. K., Lane M. D. Acetyl coenzyme A carboxylase. Purification and properties of the bovine adipose tissue enzyme. Biochemistry. 1972 Sep 26;11(20):3779–3786. doi: 10.1021/bi00770a017. [DOI] [PubMed] [Google Scholar]
  15. Pohl S. L., Birnbaumer L., Rodbell M. The glucagon-sensitive adenyl cyclase system in plasma membranes of rat liver. I. Properties. J Biol Chem. 1971 Mar 25;246(6):1849–1856. [PubMed] [Google Scholar]
  16. Qureshi A. A., Jenik R. A., Kim M., Lornitzo F. A., Porter J. W. Separation of two active forms (holo-a and holo-b) of pigeon liver fatty acid synthetase and their interconversion by phosphorylation and dephosphorylation. Biochem Biophys Res Commun. 1975 Sep 2;66(1):344–351. doi: 10.1016/s0006-291x(75)80334-2. [DOI] [PubMed] [Google Scholar]
  17. Wadke M., Brunengraber H., Lowenstein J. M., Dolhun J. J., Arsenault G. P. Fatty acid synthesis by liver perfused with deuterated and tritiated water. Biochemistry. 1973 Jul 3;12(14):2619–2624. doi: 10.1021/bi00738a011. [DOI] [PubMed] [Google Scholar]

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