Kuttner R E, Schumer W, Apantaku F O
Circ Shock. 1982;9(1):37-45.
The acceleration of glycolysis by the Embden-Meyerhof pathway (EMP) in endotoxic and septic states and its counteraction by glucocorticoids has been demonstrated by past research. Although the glycolytic contribution of the hexose monophosphate (HMP) shunt is minor, its response during endotoxemia, if similar to that of EMP, could be theoretical interest, Fasted male rats (150-260 gm) were sacrificed at 5 hr after IV injection of E coli endotoxin in dosages of 2 or 3 mg/100 gm rat weight: LD50 (Nm= 15). A second group received 1 mg dexamethasone (DMS) IV per 100 gm rat weight simultaneously with endotoxin (N = 15). Livers were homogenized in 0.25 M cold sucrose and centrifuged at 15,000 g for 20 min. Specific activity of glucose-6-phosphate dehydrogenase (G6PDH) in control livers (N = 17) was 7.1 nmoles of substrate consumed per min/mg biuret protein. Endotoxin raised G6PDH activity by 49% to 10.64 units, and the endotoxin-DMS-protected group was 6.0 units. Levels of 6-phosphogluconate (6PG) were also measured in frozen liver biopsies from similar groups of rats. Liver 6PG concentrations of control (N = 15), endotoxic (N = 15), and endotoxified-DMS-treated (N = 9) groups were 22.5, 14.3, and 17.6 nmoles/gm wet tissue, respectively. The data indicate a significant 36% acceleration in 6PG consumption during endotoxemia, which is not blocked by DMS. The cofactor, nicotinamide adenine dinucleotide phosphate (NADP), decreased significantly by 18% from the control level of 152 nmoles/gm liver (N = 9) during endotoxemia, and this fall was not corrected by DMS. In a small group (N = 6), sedoheptulose-7-phosphate declined from the control value of 76 nmoles/gm wet liver by 38% after endotoxification. It is concluded that endotoxin stimulates G6PDH, the initial enzyme of the HMP pathway, and accelerates consumption of several intermediates, Glucocorticoid prevents the enzyme activity increase but does not restore 6PC and NADP concentrations to normal levels, suggesting that different enzyme sites along the HMP shunt may have unequal responses to DMS.
过去的研究已证实，在内毒素血症和脓毒症状态下，糖酵解通过糖酵解途径（EMP）加速，而糖皮质激素可对其产生拮抗作用。尽管磷酸己糖（HMP）支路对糖酵解的贡献较小，但其在内毒素血症期间的反应（若与EMP类似）可能具有理论研究价值。将禁食的雄性大鼠（体重150 - 260克）在静脉注射剂量为2或3毫克/100克大鼠体重的大肠杆菌内毒素后5小时处死：半数致死量（Nm = 15）。第二组每100克大鼠体重静脉注射1毫克地塞米松（DMS），同时注射内毒素（N = 15）。将肝脏在0.25 M冷蔗糖中匀浆，并在15,000 g下离心20分钟。对照肝脏（N = 17）中葡萄糖-6-磷酸脱氢酶（G6PDH）的比活性为每分钟每毫克双缩脲蛋白消耗7.1纳摩尔底物。内毒素使G6PDH活性提高49%，达到10.64单位，而内毒素-DMS保护组为6.0单位。还在类似组大鼠的冷冻肝脏活检样本中测量了6-磷酸葡萄糖酸（6PG）的水平。对照（N = 15）、内毒素血症（N = 15）和内毒素血症-DMS治疗组（N = 9）的肝脏6PG浓度分别为22.5、14.3和17.6纳摩尔/克湿组织。数据表明，内毒素血症期间6PG消耗显著加速36%，且不受DMS的阻断。辅因子烟酰胺腺嘌呤二核苷酸磷酸（NADP）在内毒素血症期间从对照水平152纳摩尔/克肝脏（N = 9）显著下降18%，且这种下降未被DMS纠正。在一小群（N = 6）大鼠中，内毒素血症后景天庚酮糖-7-磷酸从对照值76纳摩尔/克湿肝脏下降了38%。结论是，内毒素刺激HMP途径的初始酶G6PDH，并加速几种中间产物的消耗。糖皮质激素可防止酶活性增加，但不能将6PC和NADP浓度恢复到正常水平，这表明HMP支路沿线的不同酶位点对DMS的反应可能不同。
