乙醇降低肝脏中果糖2,6 -二磷酸浓度的机制。
The mechanism by which ethanol decreases the concentration of fructose 2,6-bisphosphate in the liver.
作者信息
Van Schaftingen E, Bartrons R, Hers H G
出版信息
Biochem J. 1984 Sep 1;222(2):511-8. doi: 10.1042/bj2220511.
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.
给喂食后的大鼠胃内注射乙醇，在大约1小时内，其肝脏中的果糖-2,6-二磷酸浓度降低了20倍，果糖-2,6-二磷酸酶被激活，磷酸果糖激酶-2失活，但环磷酸腺苷浓度没有变化。在乙醇存在的情况下培养分离的肝细胞，导致sn-甘油-3-磷酸浓度迅速增加，果糖-2,6-二磷酸浓度缓慢持续下降，而6-磷酸己糖浓度没有变化。果糖-2,6-二磷酸酶也有相对缓慢的激活，磷酸果糖激酶-2失活。甘油和乙醛对分离的肝细胞中磷酸酯浓度的影响与乙醇相似。4-甲基吡唑消除了乙醇的作用，但增强了乙醛的作用。高浓度的葡萄糖或二羟基丙酮导致6-磷酸己糖浓度增加，并抵消了乙醇降低果糖-2,6-二磷酸浓度的作用。通常，6-磷酸己糖对肝脏中果糖-2,6-二磷酸浓度有正向作用，sn-甘油-3-磷酸有负向作用，因此，在给定的6-磷酸己糖浓度下，果糖-2,6-二磷酸浓度与sn-甘油-3-磷酸浓度呈反比关系。这些作用可以用sn-甘油-3-磷酸抑制磷酸果糖激酶-2以及抵消果糖-6-磷酸对果糖-2,6-二磷酸酶的抑制作用来解释。sn-甘油-3-磷酸还具有加速环磷酸腺苷依赖性蛋白激酶使磷酸果糖激酶-2失活的特性，而果糖-2,6-二磷酸则有相反的作用。因此，磷酸果糖激酶-2和果糖-2,6-二磷酸酶活性的变化似乎是果糖-2,6-二磷酸浓度降低的结果而非原因。
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