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大鼠肝细胞中由[2-13C]丙酮酸生成D-葡萄糖:酶对酶通道化的意义

D-glucose generation from [2-13C]pyruvate in rat hepatocytes: implications in terms of enzyme-to-enzyme channelling.

作者信息

Malaisse W J, Zhang T M, Verbruggen I, Willem R

机构信息

Laboratory of Experimental Medicine, Brussels Free University (ULB), Belgium.

出版信息

Arch Biochem Biophys. 1996 Aug 15;332(2):341-51. doi: 10.1006/abbi.1996.0351.

DOI:10.1006/abbi.1996.0351
PMID:8806744
Abstract

In rat hepatocytes exposed to [2-13C]pyruvate, newly formed glucose was more efficiently labeled in the carbon C5 than C2, as well as in the carbon C6 than C1, suggesting enzyme-to-enzyme channeling of D-glyceraldehyde 3-phosphate between glyceraldehyde-3-phosphate dehydrogenase and phosphofructoaldolase. Likewise the C1/C2 and C6/C5 ratios for 13C abundance in newly formed glucose, which largely exceeded the C3/C2 ratio of lactate or alanine and could reflect reversibility in the fumarase reaction, were compatible with the enzyme-to-enzyme tunneling of symmetrical Krebs cycle intermediates in the sequence of reactions catalyzed by succinyl-CoA synthetase, succinate dehydrogenase, and fumarase. This study further indicates that the major fraction of pyruvate is metabolized via pyruvate carboxylase rather than pyruvate dehydrogenase.

摘要

在暴露于[2-¹³C]丙酮酸的大鼠肝细胞中,新形成的葡萄糖在C5碳位比C2碳位更有效地被标记,在C6碳位比C1碳位更有效地被标记,这表明3-磷酸甘油醛在甘油醛-3-磷酸脱氢酶和磷酸果糖醛缩酶之间存在酶到酶的通道化作用。同样,新形成的葡萄糖中¹³C丰度的C1/C2和C6/C5比率,大大超过了乳酸或丙氨酸的C3/C2比率,并且可以反映富马酸酶反应的可逆性,这与琥珀酰辅酶A合成酶、琥珀酸脱氢酶和富马酸酶催化的反应序列中对称三羧酸循环中间体的酶到酶隧道效应是一致的。这项研究进一步表明,丙酮酸的主要部分是通过丙酮酸羧化酶而不是丙酮酸脱氢酶进行代谢的。

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