Skip to main content
PMC home page
Biochemical Journal logoLink to Biochemical Journal
. 1991 Dec 15;280(Pt 3):733–737. doi: 10.1042/bj2800733

The short-term regulation of hepatic acetyl-CoA carboxylase during starvation and re-feeding in the rat.

M R Munday 1, M R Milic 1, S Takhar 1, M J Holness 1, M C Sugden 1
PMCID: PMC1130515  PMID: 1684893

Abstract

Rapid inhibition of acetyl-CoA carboxylase (ACC) activity in rat liver in response to 6 h starvation and rapid re-activation in response to 2-6 h of re-feeding chow were shown to be due to changes in the expressed activity of existing enzyme. Decreases and increases in ACC concentration occurred at later stages of the transitions, i.e. 6-48 h starvation and 8-24 h re-feeding respectively. The decrease in expressed activity of ACC was due primarily to changes in its phosphorylation state, demonstrated by a significantly decreased Vmax. and significantly increased Ka for citrate of enzyme purified by avidin-Sepharose chromatography from 6 h- or 48 h-starved rats. These effects were totally reversed within 2-4 h of chow re-feeding. Changes in the activity of purified ACC closely correlated with reciprocal changes in the activity of AMP-activated protein kinase (AMP-PK) over the fed to starved to re-fed transition. Increases in the activity ratio of cyclic-AMP-dependent protein kinase in response to starvation lagged behind the increase in AMP-PK and the decrease in ACC activity. Changes in AMP-PK and ACC activities of rat liver closely correlated with changes in plasma insulin concentration in response to time courses of starvation and re-feeding.

Full text

PDF
733

Selected References

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

  1. Blackmore P. F., Exton J. H. Studies on the hepatic calcium-mobilizing activity of aluminum fluoride and glucagon. Modulation by cAMP and phorbol myristate acetate. J Biol Chem. 1986 Aug 25;261(24):11056–11063. [PubMed] [Google Scholar]
  2. Borthwick A. C., Edgell N. J., Denton R. M. Use of rapid gel-permeation chromatography to explore the inter-relationships between polymerization, phosphorylation and activity of acetyl-CoA carboxylase. Effects of insulin and phosphorylation by cyclic AMP-dependent protein kinase. Biochem J. 1987 Feb 1;241(3):773–782. doi: 10.1042/bj2410773. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Carling D., Zammit V. A., Hardie D. G. A common bicyclic protein kinase cascade inactivates the regulatory enzymes of fatty acid and cholesterol biosynthesis. FEBS Lett. 1987 Nov 2;223(2):217–222. doi: 10.1016/0014-5793(87)80292-2. [DOI] [PubMed] [Google Scholar]
  4. Davies S. P., Sim A. T., Hardie D. G. Location and function of three sites phosphorylated on rat acetyl-CoA carboxylase by the AMP-activated protein kinase. Eur J Biochem. 1990 Jan 12;187(1):183–190. doi: 10.1111/j.1432-1033.1990.tb15293.x. [DOI] [PubMed] [Google Scholar]
  5. Geelen M. J., Hindriks G. A. Studies on the substrate for hepatic lipogenesis in the rat. FEBS Lett. 1984 Sep 17;175(1):8–12. doi: 10.1016/0014-5793(84)80558-x. [DOI] [PubMed] [Google Scholar]
  6. Goodridge A. G., Back D. W., Wilson S. B., Goldman M. J. Regulation of genes for enzymes involved in fatty acid synthesis. Ann N Y Acad Sci. 1986;478:46–62. doi: 10.1111/j.1749-6632.1986.tb15520.x. [DOI] [PubMed] [Google Scholar]
  7. Hardie D. G. Regulation of fatty acid synthesis via phosphorylation of acetyl-CoA carboxylase. Prog Lipid Res. 1989;28(2):117–146. doi: 10.1016/0163-7827(89)90010-6. [DOI] [PubMed] [Google Scholar]
  8. Haystead T. A., Moore F., Cohen P., Hardie D. G. Roles of the AMP-activated and cyclic-AMP-dependent protein kinases in the adrenaline-induced inactivation of acetyl-CoA carboxylase in rat adipocytes. Eur J Biochem. 1990 Jan 12;187(1):199–205. doi: 10.1111/j.1432-1033.1990.tb15295.x. [DOI] [PubMed] [Google Scholar]
  9. Holness M. J., MacLennan P. A., Palmer T. N., Sugden M. C. The disposition of carbohydrate between glycogenesis, lipogenesis and oxidation in liver during the starved-to-fed transition. Biochem J. 1988 Jun 1;252(2):325–330. doi: 10.1042/bj2520325. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Holness M. J., Sugden M. C. Hepatic carbon flux after re-feeding. Hyperthyroidism blocks glycogen synthesis and the suppression of glucose output observed in response to carbohydrate re-feeding. Biochem J. 1987 Nov 1;247(3):627–634. doi: 10.1042/bj2470627. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Majerus P. W., Kilburn E. Acetyl coenzyme A carboxylase. The roles of synthesis and degradation in regulation of enzyme levels in rat liver. J Biol Chem. 1969 Nov 25;244(22):6254–6262. [PubMed] [Google Scholar]
  12. Moir A. M., Zammit V. A. Changes in the properties of cytosolic acetyl-CoA carboxylase studied in cold-clamped liver samples from fed, starved and starved-refed rats. Biochem J. 1990 Dec 1;272(2):511–517. doi: 10.1042/bj2720511. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Munday M. R., Campbell D. G., Carling D., Hardie D. G. Identification by amino acid sequencing of three major regulatory phosphorylation sites on rat acetyl-CoA carboxylase. Eur J Biochem. 1988 Aug 1;175(2):331–338. doi: 10.1111/j.1432-1033.1988.tb14201.x. [DOI] [PubMed] [Google Scholar]
  14. Munday M. R., Carling D., Hardie D. G. Negative interactions between phosphorylation of acetyl-CoA carboxylase by the cyclic AMP-dependent and AMP-activated protein kinases. FEBS Lett. 1988 Aug 1;235(1-2):144–148. doi: 10.1016/0014-5793(88)81251-1. [DOI] [PubMed] [Google Scholar]
  15. Munday M. R., Hardie D. G. The role of acetyl-CoA carboxylase phosphorylation in the control of mammary gland fatty acid synthesis during the starvation and re-feeding of lactating rats. Biochem J. 1986 Jul 1;237(1):85–91. doi: 10.1042/bj2370085. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Nishikori K., Iritani N., Numa S. Levels of acetyl coenzyme A carboxylase and its effectors in rat liver after short-term fat-free refeeding. FEBS Lett. 1973 May 15;32(1):19–21. doi: 10.1016/0014-5793(73)80725-2. [DOI] [PubMed] [Google Scholar]
  17. Resink T. J., Hemmings B. A., Tung H. Y., Cohen P. Characterisation of a reconstituted Mg-ATP-dependent protein phosphatase. Eur J Biochem. 1983 Jun 15;133(2):455–461. doi: 10.1111/j.1432-1033.1983.tb07485.x. [DOI] [PubMed] [Google Scholar]
  18. Roman-Lopez C. R., Shriver B. J., Joseph C. R., Allred J. B. Mitochondrial acetyl-CoA carboxylase. Time course of mobilization/activation in liver of refed rats. Biochem J. 1989 Jun 15;260(3):927–930. doi: 10.1042/bj2600927. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Roskoski R., Jr Assays of protein kinase. Methods Enzymol. 1983;99:3–6. doi: 10.1016/0076-6879(83)99034-1. [DOI] [PubMed] [Google Scholar]
  20. Seitz H. J., Müller M. J., Krone W., Tarnowski W. Coordinate control of intermediary metabolism in rat liver by the insulin/glucagon ratio during starvation and after glucose refeeding. Regulatory significance of long-chain acyl-CoA and cyclic AMP. Arch Biochem Biophys. 1977 Oct;183(2):647–663. doi: 10.1016/0003-9861(77)90399-x. [DOI] [PubMed] [Google Scholar]
  21. Sim A. T., Hardie D. G. The low activity of acetyl-CoA carboxylase in basal and glucagon-stimulated hepatocytes is due to phosphorylation by the AMP-activated protein kinase and not cyclic AMP-dependent protein kinase. FEBS Lett. 1988 Jun 20;233(2):294–298. doi: 10.1016/0014-5793(88)80445-9. [DOI] [PubMed] [Google Scholar]
  22. Sugden M. C., Liu Y. L., Holness M. J. Glucose utilization and disposal in cardiothoracic and skeletal muscles during the starved-to-fed transition in the rat. Biochem J. 1990 Nov 15;272(1):133–137. doi: 10.1042/bj2720133. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Thampy K. G., Wakil S. J. Regulation of acetyl-coenzyme A carboxylase. II. Effect of fasting and refeeding on the activity, phosphate content, and aggregation state of the enzyme. J Biol Chem. 1988 May 5;263(13):6454–6458. [PubMed] [Google Scholar]
  24. Witters L. A., Watts T. D., Daniels D. L., Evans J. L. Insulin stimulates the dephosphorylation and activation of acetyl-CoA carboxylase. Proc Natl Acad Sci U S A. 1988 Aug;85(15):5473–5477. doi: 10.1073/pnas.85.15.5473. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

RESOURCES