Bielicki L, Krieglstein J, Wever K
Arzneimittelforschung. 1980;30(4):594-7.
It has been demonstrated in previous work that hexokinase is solubilized from the mitochondrial membrane in anesthesia. In the present investigation this effect was strongly correlated with the surgical stage of anesthesia by the application of thiopental to rats (80 mg/kg), mice (100 mg/kg) and guinea pigs (32 mg/kg). The solubilization of hexokinase was demonstrable, too, in different areas of rat brains under thiopental treatment (80 mg/kg). In order to elevate the cerebral concentration of glucose 6-phosphate, which is the most potent substrate for the solubilization of bound hexokinase, male Sprague-Dawley rats were pretreated with the antimetabolite 6-aminonicotinamide (6-AN). After i.p. injection of 6-AN (35 mg/kg) we measured an increased activity of soluble brain hexokinase in the same order of magnitude as it was determined in anesthesia. Thiopental application did not show a further significant increase. A solubilization of hexokinase activity by 6-AN was not measurable in vitro. Furthermore, we examined the other key enzymes in the glycolytic pathway. We found a competitive inhibition of phosphofrucktokinase activity by thiopental, but no inhibition of hexokinase and pyruvate-kinase activity.
先前的研究表明，在麻醉状态下己糖激酶可从线粒体膜上溶解下来。在本研究中，通过给大鼠（80毫克/千克）、小鼠（100毫克/千克）和豚鼠（32毫克/千克）注射硫喷妥钠，这种效应与麻醉的手术阶段密切相关。在硫喷妥钠（80毫克/千克）处理的大鼠大脑不同区域，也可证实己糖激酶的溶解。为了提高葡萄糖6-磷酸的脑内浓度，葡萄糖6-磷酸是溶解结合型己糖激酶的最有效底物，对雄性斯普拉格-道利大鼠预先给予抗代谢物6-氨基烟酰胺（6-AN）。腹腔注射6-AN（35毫克/千克）后，我们测得可溶性脑己糖激酶活性增加，其增加幅度与在麻醉状态下测得的相当。硫喷妥钠的应用并未显示出进一步的显著增加。在体外无法检测到6-AN对己糖激酶活性的溶解作用。此外，我们还检测了糖酵解途径中的其他关键酶。我们发现硫喷妥钠对磷酸果糖激酶活性有竞争性抑制作用，但对己糖激酶和丙酮酸激酶活性无抑制作用。
