Summary
The activity of liver glucokinase is controlled in the short term by the concentration of its substrate glucose and by a regulatory protein, which acts as a competitive inhibitor with respect to glucose. In mammalian species, the effect of this protein is modulated by fructose 6-phosphate, which reinforces the inhibition, and by fructose 1-phosphate which antagonizes it. In the rat, the regulatory protein is found in the two tissues that express glucokinase, i.e., the liver and the pancreatic islets. Of particular interest is the fact that the regulatory protein is absent from the liver in those species that have no hepatic glucokinase. These results indicate that the two proteins form a functional unit. The regulatory protein appears in rat liver before birth, whereas glucokinase is only synthesized after 15 days of extrauterine life. The concentration of regulatory protein in the liver of the adult rat decreases by about 50% during starvation and in diabetes mellitus. Under these conditions, the difference between the concentrations of regulatory protein and glucokinase remains constant at about 0.4–0.5 nmol/g.
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Abbreviations
- Fructose 1-P:
-
fructose 1-phosphate
- DEAE:
-
diethylaminoethyl
- glucose 6-P:
-
glucose 6-phosphate
References
Colowick SP (1973) The hexokinases. In: Boyer P (ed) The enzymes. 3rd edn Vol 9. Academic Press, New York, pp. 1–48
Weinhouse S (1976) Regulation of glucokinase in liver. Curr Top Cell Regul 11: 1–50
Iynedjian P (1993) Mammalian glucokinase and its gene. Biochem J 293: 1–13
Randle PJ (1993) Glucokinase and candidate genes for type 2 (non-insulin-dependent) diabetes mellitus. Diabetologia 36: 269–275
Thorens B, Sarkar HK, Kaback HR, Lodish JF (1988) Cloning and functional expression in bacteria of a novel glucose transporter present in liver, intestine, kidney, and β-pancreatic islet cells. Cell 55: 281–290
Permutt MA, Chiu KC, Tanizawa Y (1992) Glucokinase and NIDDM. A candidate gene that paid off. Diabetes 41: 1367–1372
Bell GI, Froguel P, Nishi S et al. (1993) Mutations of the glucokinase gene and diabetes mellitus. Trends Endocrinol Metab 4: 86–90
Pollard-Knight D, Cornish-Bowden A (1982) Mechanism of liver glucokinase. Mol Cell Biochem 44: 71–80
Dawson CM, Hales CN (1969) The inhibition of rat liver glucokinase by palmitoyl-CoA. Biochim Biophys Acta 176: 657–659
Tippett PS, Neet KE (1982) Specific inhibition of glucokinase by long chain acyl coenzymes A below the critical micelle concentration. J Biol Chem 257: 12839–12845
Hue L, Maisin L, Rider MH (1988) Palmitate inhibits liver glycolysis. Involvement of fructose 2,6-bisphosphate in the glucose/fatty acid cycle. Biochem J 251: 541–545
Van Schaftingen E (1993) Glycolysis revisited. Diabetologia 36: 581–588
Clark DG, Filsell OH, Topping DL (1979) Effects of fructose concentration on carbohydrate metabolism, heat production and substrate cycling in isolated rat hepatocytes. Biochem J 184: 501–507
Van Schaftingen E, Vandercammen A (1989) Stimulation of glucose phosphorylation by fructose in isolated rat hepatocytes. Eur J Biochem 179: 173–177
Van Schaftingen E (1989) A protein from rat liver confers to glucokinase the property of being antagonistically regulated by fructose 6-phosphate and fructose 1-phosphate. Eur J Biochem 179: 179–184
Vandercammen A, Van Schaftingen E (1990) The mechanism by which rat liver glucokinase is inhibited by the regulatory protein. Eur J Biochem 191: 483–489
Detheux M, Vanderkerckhove J, Van Schaftingen E (1993) Cloning and sequencing of rat liver cDNAs encoding the regulatory protein of glucokinase. FEBS Lett 321: 111–115
Vandercammen A, Van Schaftingen E (1993) Species and tissue distribution of the regulatory protein of glucokinase. Biochem J 294: 551–556
Malaisse WJ, Malaisse-Lagae F, Davies DR, Vandercammen A, Van Schaftingen E (1990) Regulation of glucokinase by a fructose-1-phosphate-sensitive protein in pancreatic islets. Eur J Biochem 190: 539–545
Detheux M, Vandercammen A, Van Schaftingen E (1991) Effectors of the regulatory protein acting on liver glucokinase: a kinetic investigation. Eur J Biochem 200: 553–561
Andreone TL, Printz RL, Pilkis SJ, Magnuson MA, Granner DK (1989) The amino acid sequence of rat liver glucokinase deduced from cloned cDNA. J Biol Chem 264: 363–369
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Van Schaftingen, E. Short-term regulation of glucokinase. Diabetologia 37 (Suppl 2), S43–S47 (1994). https://doi.org/10.1007/BF00400825
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DOI: https://doi.org/10.1007/BF00400825