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. 1984 Sep 1;222(2):511–518. doi: 10.1042/bj2220511

The mechanism by which ethanol decreases the concentration of fructose 2,6-bisphosphate in the liver.

E Van Schaftingen, R Bartrons, H G Hers
PMCID: PMC1144206  PMID: 6089771

Abstract

The intragastric administration of ethanol to fed rats caused in their liver, within about 1 h, a 20-fold decrease in the concentration of fructose 2,6-bisphosphate, an activation of fructose 2,6-bisphosphatase, an inactivation of phosphofructo-2-kinase but no change in the concentration of cyclic AMP. Incubation of isolated hepatocytes in the presence of ethanol caused a rapid increase in the concentration of sn-glycerol 3-phosphate and a slower and continuous decrease in the concentration of fructose 2,6-bisphosphate with no change in that of hexose 6-phosphates. There was also a relatively slow activation of fructose 2,6-bisphosphatase and inactivation of phosphofructo-2-kinase. Glycerol and acetaldehyde had effects similar to those of ethanol on the concentration of phosphoric esters in the isolated liver cells. 4-Methylpyrazole cancelled the effect of ethanol but reinforced those of acetaldehyde. High concentrations of glucose or of dihydroxyacetone caused an increase in the concentration of hexose 6-phosphates and counteracted the effect of ethanol to decrease the concentration of fructose 2,6-bisphosphate. As a rule, hexose 6-phosphates had a positive effect and sn-glycerol 3-phosphate had a negative effect on the concentration of fructose 2,6-bisphosphate in the liver, so that, at a given concentration of hexose 6-phosphates, there was an inverse relationship between the concentration of fructose 2,6-bisphosphate and that of sn-glycerol 3-phosphate. These effects could be explained by the ability of sn-glycerol 3-phosphate to inhibit phosphofructo-2-kinase and to counteract the inhibition of fructose 2,6-bisphosphatase by fructose 6-phosphate. sn-Glycerol 3-phosphate had also the property to accelerate the inactivation of phosphofructo-2-kinase by cyclic AMP-dependent protein kinase whereas fructose 2,6-bisphosphate had the opposite effect. The changes in the activity of phosphofructo-2-kinase and fructose 2,6-bisphosphatase appear therefore to be the result rather than the cause of the decrease in the concentration of fructose 2,6-bisphosphate.

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Selected References

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  1. Bartrons R., Hue L., Van Schaftingen E., Hers H. G. Hormonal control of fructose 2,6-bisphosphate concentration in isolated rat hepatocytes. Biochem J. 1983 Sep 15;214(3):829–837. doi: 10.1042/bj2140829. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bartrons R., Van Schaftingen E., Hers H. G. The ability of adenosine to decrease the concentration of fructose 2,6-bisphosphate in isolated hepatocytes. A cyclic AMP-mediated effect. Biochem J. 1984 Feb 15;218(1):157–163. doi: 10.1042/bj2180157. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Claus T. H., Schlumpf J. R., El-Maghrabi M. R., Pilkis S. J. Regulation of the phosphorylation and activity of 6-phosphofructo 1-kinase in isolated hepatocytes by alpha-glycerolphosphate and fructose 2,6-bisphosphate. J Biol Chem. 1982 Jul 10;257(13):7541–7548. [PubMed] [Google Scholar]
  4. Deitrich R. A., Troxell P. A., Worth W. S. Inhibition of aldehyde dehydrogenase in brain and liver by cyanamide. Biochem Pharmacol. 1976 Dec 15;25(24):2733–2737. doi: 10.1016/0006-2952(76)90265-3. [DOI] [PubMed] [Google Scholar]
  5. El-Maghrabi M. R., Claus T. H., Pilkis J., Fox E., Pilkis S. J. Regulation of rat liver fructose 2,6-bisphosphatase. J Biol Chem. 1982 Jul 10;257(13):7603–7607. [PubMed] [Google Scholar]
  6. El-Maghrabi M. R., Fox E., Pilkis J., Pilkis S. J. Cyclic AMP-dependent phosphorylation of rat liver 6-phosphofructo 2-kinase, fructose 2,6-bisphosphatase. Biochem Biophys Res Commun. 1982 Jun 15;106(3):794–802. doi: 10.1016/0006-291x(82)91780-6. [DOI] [PubMed] [Google Scholar]
  7. Hers H. G., Van Schaftingen E. Fructose 2,6-bisphosphate 2 years after its discovery. Biochem J. 1982 Jul 15;206(1):1–12. doi: 10.1042/bj2060001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Hue L., Blackmore P. F., Shikama H., Robinson-Steiner A., Exton J. H. Regulation of fructose-2,6-bisphosphate content in rat hepatocytes, perfused hearts, and perfused hindlimbs. J Biol Chem. 1982 Apr 25;257(8):4308–4313. [PubMed] [Google Scholar]
  9. Hue L., Felíu J. E., Hers H. G. Control of gluconeogenesis and of enzymes of glycogen metabolism in isolated rat hepatocytes. A parallel study of the effect of phenylephrine and of glucagon. Biochem J. 1978 Dec 15;176(3):791–797. doi: 10.1042/bj1760791. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Krebs H. A., Freedland R. A., Hems R., Stubbs M. Inhibition of hepatic gluconeogenesis by ethanol. Biochem J. 1969 Mar;112(1):117–124. doi: 10.1042/bj1120117. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Makar A. B., Mannering G. J. Kinetics of ethanol metabolism in the intact rat and monkey. Biochem Pharmacol. 1970 Jun;19(6):2017–2022. doi: 10.1016/0006-2952(70)90298-4. [DOI] [PubMed] [Google Scholar]
  12. NIKKILAE E. A., OJALA K. ROLE OF HEPATIC L-ALPHA-GLYCEROPHOSPHATE AND TRIGLYCERIDE SYNTHESIS IN PRODUCTION OF FATTY LIVER BY ETHANOL. Proc Soc Exp Biol Med. 1963 Aug-Sep;113:814–817. doi: 10.3181/00379727-113-28499. [DOI] [PubMed] [Google Scholar]
  13. Probst I., Jungermann K. Short-term regulation of glycolysis by insulin and dexamethasone in cultured rat hepatocytes. Eur J Biochem. 1983 Sep 1;135(1):151–156. doi: 10.1111/j.1432-1033.1983.tb07630.x. [DOI] [PubMed] [Google Scholar]
  14. Rognstad R., Katz J. Effects of hormones and of ethanol on the fructose 6-P-fructose 1,6-P2 futile cycle during gluconeogenesis in the liver. Arch Biochem Biophys. 1976 Dec;177(2):337–345. doi: 10.1016/0003-9861(76)90447-1. [DOI] [PubMed] [Google Scholar]
  15. Seglen P. O. Preparation of rat liver cells. 3. Enzymatic requirements for tissue dispersion. Exp Cell Res. 1973 Dec;82(2):391–398. doi: 10.1016/0014-4827(73)90357-1. [DOI] [PubMed] [Google Scholar]
  16. Sener A., Van Schaftingen E., Van de Winkel M., Pipeleers D. G., Malaisse-Lagae F., Malaisse W. J., Hers H. G. Effects of glucose and glucagon on the fructose 2,6-bisphosphate content of pancreatic islets and purified pancreatic B-cells. A comparison with isolated hepatocytes. Biochem J. 1984 Aug 1;221(3):759–764. doi: 10.1042/bj2210759. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Steiner A. L., Parker C. W., Kipnis D. M. Radioimmunoassay for cyclic nucleotides. I. Preparation of antibodies and iodinated cyclic nucleotides. J Biol Chem. 1972 Feb 25;247(4):1106–1113. [PubMed] [Google Scholar]
  18. Theorell H., Yonetani T., Sjöberg B. On the effects of some heterocyclic compounds on the enzymic activity of liver alcohol dehydrogenase. Acta Chem Scand. 1969;23(1):255–260. doi: 10.3891/acta.chem.scand.23-0255. [DOI] [PubMed] [Google Scholar]
  19. Thurman R. G., Scholz R. Interaction of glycolysis and respiration in perfused rat liver. Changes in oxygen uptake following the addition of ethanol. Eur J Biochem. 1977 May 2;75(1):13–21. doi: 10.1111/j.1432-1033.1977.tb11499.x. [DOI] [PubMed] [Google Scholar]
  20. Van Schaftingen E., Davies D. R., Hers H. G. Inactivation of phosphofructokinase 2 by cyclic AMP - dependent protein kinase. Biochem Biophys Res Commun. 1981 Nov 16;103(1):362–368. doi: 10.1016/0006-291x(81)91701-0. [DOI] [PubMed] [Google Scholar]
  21. Van Schaftingen E., Hue L., Hers H. G. Control of the fructose-6-phosphate/fructose 1,6-bisphosphate cycle in isolated hepatocytes by glucose and glucagon. Role of a low-molecular-weight stimulator of phosphofructokinase. Biochem J. 1980 Dec 15;192(3):887–895. doi: 10.1042/bj1920887. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Van Schaftingen E., Lederer B., Bartrons R., Hers H. G. A kinetic study of pyrophosphate: fructose-6-phosphate phosphotransferase from potato tubers. Application to a microassay of fructose 2,6-bisphosphate. Eur J Biochem. 1982 Dec;129(1):191–195. doi: 10.1111/j.1432-1033.1982.tb07039.x. [DOI] [PubMed] [Google Scholar]
  23. van Schaftingen E., Davies D. R., Hers H. G. Fructose-2,6-bisphosphatase from rat liver. Eur J Biochem. 1982 May;124(1):143–149. doi: 10.1111/j.1432-1033.1982.tb05917.x. [DOI] [PubMed] [Google Scholar]

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