van Schaftingen E, Vandercammen A, Detheux M, Davies D R
Laboratory of Physiological Chemistry, International Institute of Cellular and Molecular Pathology, Brussels, Belgium.
Adv Enzyme Regul. 1992;32:133-48. doi: 10.1016/0065-2571(92)90013-p.
Fructose, sorbitol and D-glyceraldehyde stimulate the rate of glucose phosphorylation in isolated hepatocytes. This effect is mediated by fructose 1-phosphate, which releases the inhibition exerted by a regulatory protein on liver glucokinase. In the presence of fructose 6-phosphate, the regulatory protein binds to, and inhibits, liver glucokinase. Fructose 1-phosphate antagonizes this inhibition by causing dissociation of the glucokinase-regulatory protein complex. Both phosphate esters act by binding to the regulatory protein, and by presumably causing changes in its conformation. The regulatory protein behaves as a fully competitive inhibitor. It inhibits liver glucokinase from various species, and rat islet glucokinase, but has no effect on hexokinases from mammalian tissues or from yeast, or on glucokinase from microorganisms. Kinetic studies indicate that the regulatory protein binds to glucokinase at a site distinct from the catalytic site. Several phosphate esters, mainly polyol-phosphates, were found to mimick the effect of fructose 6-phosphate. The most potent is sorbitol 6-phosphate, suggesting that fructose 6-phosphate is recognized by the regulatory protein in its open-chain configuration. Other phosphate esters and Pi have a fructose 1-phosphate-like effect. The stimulatory effect of fructose on glucose phosphorylation is observed not only in isolated hepatocytes but also in the livers of anesthetized rats. This suggests that fructose could be a nutritional signal causing an increase in the hepatic glucose uptake.
果糖、山梨醇和D-甘油醛可刺激分离的肝细胞中葡萄糖磷酸化的速率。这种作用是由1-磷酸果糖介导的，它解除了一种调节蛋白对肝脏葡萄糖激酶的抑制作用。在6-磷酸果糖存在的情况下，调节蛋白会结合并抑制肝脏葡萄糖激酶。1-磷酸果糖通过引起葡萄糖激酶-调节蛋白复合物的解离来拮抗这种抑制作用。这两种磷酸酯都通过与调节蛋白结合并可能引起其构象变化而起作用。该调节蛋白表现为完全竞争性抑制剂。它抑制来自不同物种的肝脏葡萄糖激酶以及大鼠胰岛葡萄糖激酶，但对来自哺乳动物组织或酵母的己糖激酶或微生物的葡萄糖激酶没有影响。动力学研究表明，调节蛋白在与催化位点不同的位点与葡萄糖激酶结合。发现几种磷酸酯，主要是多元醇磷酸酯，可模拟6-磷酸果糖的作用。最有效的是6-磷酸山梨醇，这表明调节蛋白以其开链构型识别6-磷酸果糖。其他磷酸酯和无机磷酸具有类似1-磷酸果糖的作用。果糖对葡萄糖磷酸化的刺激作用不仅在分离的肝细胞中观察到，在麻醉大鼠的肝脏中也观察到。这表明果糖可能是一种导致肝脏葡萄糖摄取增加的营养信号。
