IDENTIFICATION OF GLUCOSE METABOLITES IN BRAIN AND THE RELATIONSHIP TO 2-DEOXYGLU

脑内葡萄糖代谢物的鉴定及其与 2-DEOXYGLU 的关系

• 批准号: 3822954
• 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/3822954
• 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

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% at 20 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 are not sufficient to conclude the quantitative aspect of the dephosphorylation of glucose-6-phosphate.

大鼠脑内葡萄糖-6-磷酸去磷酸化的程度 在这份报告中，对vivo进行了重新审查。从质量上讲，反应是 通过比较脑和脑中~3H-葡萄糖/~(14)C-葡萄糖的比值进行检查 注射[2-~3H]-和[U-14C]-葡萄糖后1~10分钟内采血。 目前的发现表明，我们之前的结果是~3H/14C降低了35% 注射后5分钟脑部葡萄糖比率由 在分离过程中，未检测到的污染物与葡萄糖一起洗脱。 在本研究中使用改进的分馏程序，我们发现 脑葡萄糖中~3H/~(14)C比率的下降速度是 显著大于血糖，斜率的差异 两个疗程的总有效率为29%。从数量上讲，蛋白的去磷酸化 从第一分钟内获得的数据研究葡萄糖-6-磷酸 在注射示踪剂之后。放射性代谢物的形成 来自[2-~3H]-葡萄糖的含量显著高于来自[U-14C]-葡萄糖的含量 注射后即刻，S 10岁时25%，S 20岁时21%，S 20时14% S注射后30分钟。这一下降趋势是由于损失了 氚化水促进血液循环。葡萄糖利用率 从放射性代谢物的初始形成速度计算 从[2-~3H]-葡萄糖得1.04微克/分/克；从[U-14C]-葡萄糖得0.83 Umol/min/g。0.21mol/min/g的差异归因于 大脑中葡萄糖-6-磷酸的去磷酸化。最新发现 重申我们之前的结论，在大脑中，去磷酸化的 葡萄糖-6-磷酸具有活性。因为葡萄糖周转速度很快 大脑和体内标记葡萄糖的快速平衡 通过血液循环，注射后2分钟获得的数据不会 足以得出结论的数量方面的去磷酸化 葡萄糖-6-磷酸。