GLUCOSE METABOLITES IN BRAIN AND THE RELATIONSHIP TO 2-DEOXYGLUCOSE METHOD

脑内葡萄糖代谢物及其与2-脱氧葡萄糖法的关系

• 批准号: 3821228
• 负责人: M-T HUANG
• 金额: --
• 依托单位: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3821228
• 关键词: anions; bioenergetics; brain metabolism; cations; chromatography; deoxyglucose; glucose; glucose 6 phosphate; glucose metabolism; hexokinase; ion exchange chromatography; lyophilization; paper chromatography; phosphorylation; radiodiagnosis; radiotracer; tritium

The magnitude of the dephosphorylation of glucose-6-phosphate in brain in vivo was reexamined in this report. Qualitatively, the reaction was examined by comparing the ratio of 3H-glucose/14C- glucose in brain and blood from 1 to 10 min after an injection of (2-3H)- and (U-14C)-glucose. Current findings show that our previous result of a 35% decrease in 3H/14C ratio in brain glucose 5 minutes after the injection was caused by undetected contaminants coeluted with glucose in the isolation process. Using an improved fractionation procedure, in the present study, we found that the rate of decrease of the 3H/14C ratio in brain glucose is significantly greater than that in blood glucose; the difference in slopes of the two time-courses was 29%. Quantitatively, the dephosphorylation of glucose-6-phosphate was studied from data obtained within the first minute after the injection of tracers. The formation of radioactive metabolites from (2-3H)-glucose is significantly greater than from (U-14C)- glucose immediately following the injection, 25% at 10 s, 21% s, and 14% at 30 s after the injection. The decreasing trend is caused by loss of tritiated water to blood circulation. The rate of glucose utilization calculated from the initial rates of formation of radioactive metabolites from (2-3H)-glucose was 1.04 umol/min/g; from (U-14C)-glucose was 0.83 umol/min/g. The difference of 0.21 mol/min/g was attributed to the dephosphorylation of glucose-6-phosphate in brain. Current findings reaffirm our previous conclusion that in brain, the dephosphorylation of glucose-6-phosphate is active. Because of rapid rate of glucose turnover in brain and the rapid equilibration of labeled glucose in the body aided by blood circulation, data obtained 2 min after the injection as reported by Nelson et al. (Nelson, T., Lucignani, G., Atlas, S., Crane, A.M., Dienel, G.A., and Sokoloff, L.: Re-examination of glucose-6-phosphatase activity in brain in vivo: No evidence for a futile cycle. Science 229: 60-62, 1985) are not sufficient to conclude the quantitative aspect of the dephosphorylation of glucose-6-phosphate.

葡萄糖-6-磷酸去磷酸化的程度 本报告对体内大脑进行了重新检查。 定性地讲， 通过比较 3H-葡萄糖/14C-的比率来检查反应 注射后 1 至 10 分钟脑和血液中的葡萄糖 (2-3H)-和(U-14C)-葡萄糖。 目前的研究结果表明，我们的 先前结果显示脑葡萄糖 3H/14C 比率降低 35% 注射后5分钟未检测到造成 污染物在分离过程中与葡萄糖共洗脱。 在本研究中，使用改进的分馏程序， 我们发现大脑中3H/14C比值的下降率 葡萄糖明显高于血糖；这 两个时间进程的斜率差异为 29%。 定量地，葡萄糖-6-磷酸的去磷酸化是 根据事件发生后第一分钟内获得的数据进行研究 注射示踪剂。 放射性代谢物的形成 (2-3H)-葡萄糖显着大于(U-14C)- 注射后立即检测葡萄糖，10 秒时为 25%，秒后为 21%， 注射后 30 秒为 14%。 下降趋势为 由于血液循环中氚水的流失而引起。 的比率 根据初始形成速率计算的葡萄糖利用率 (2-3H)-葡萄糖的放射性代谢物的含量为 1.04 微摩尔/分钟/克； (U-14C)-葡萄糖的浓度为0.83 umol/min/g。 这 0.21 mol/min/g 的差异归因于 大脑中葡萄糖-6-磷酸的去磷酸化。 当前的 研究结果再次证实了我们之前的结论：在大脑中， 葡萄糖-6-磷酸的去磷酸化是活跃的。 由于 大脑中葡萄糖周转速度快和快速平衡 血液循环辅助下体内标记葡萄糖的含量，数据 根据 Nelson 等人的报告，注射后 2 分钟获得。 （尼尔森，T.，卢西尼亚尼，G.，阿特拉斯，S.，克兰，A.M.，迪内尔，G.A.， 和 Sokoloff, L.：葡萄糖 6 磷酸酶的重新检查 体内大脑活动：没有证据表明循环无效。 科学 229: 60-62, 1985）不足以得出定量结论 葡萄糖-6-磷酸去磷酸化的方面。