A protein from rat liver confers to glucokinase the property of being antagonistically regulated by fructose 6-phosphate and fructose 1-phosphate.
At a concentration of 1 mM, fructose 1-phosphate stimulated about twofold, and glucose 6-phosphate inhibited by about 30%, the phosphorylation of 5 mM glucose in high-speed supernatants prepared from rat liver or from isolated hepatocytes, but did not affect, or barely so, the activity of a partially purified preparation of glucokinase. Anion-exchange chromatography of liver extracts separated glucokinase from a fructose-6-phosphate-sensitive and fructose-1-phosphate-sensitive inhibitor of that enzyme. This inhibitor could be further purified by chromatography on phospho-Ultrogel. It was destroyed by trypsin and was heat-labile. It inhibited glucokinase competitively with respect to glucose and its inhibitory effect was greatly reinforced by fructose 6-phosphate although not by glucose 6-phosphate. Fructose 1-phosphate relieved the enzyme of the inhibitory effect of the regulator and antagonised the effect of fructose 6-phosphate in a competitive manner. It is concluded that the regulator plays a role in the physiological control of the activity of glucokinase, particularly with respect to the stimulatory effect of fructose in isolated hepatocytes (see preceding paper in this journal).
Van Schaftingen
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Laboratoire de Chimie Physiologique, Université Catholique de Louvain, Belgium.
D000818:Animals; D002850:Chromatography, Gel; D002852:Chromatography, Ion Exchange; D005636:Fructosephosphates / Q000494:pharmacology*; D005941:Glucokinase / Q000037:antagonists & inhibitors* / Q000302:isolation & purification; D008099:Liver / Q000378:metabolism*; D008297:Male; D011506:Proteins / Q000302:isolation & purification* / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014020:Tissue Extracts / Q000032:analysis
D005636:Fructosephosphates; D011506:Proteins; D014020:Tissue Extracts; C032284:fructose-1-phosphate; C027618:fructose-6-phosphate; D005941:Glucokinase