Misconceptions Regarding Basic Thermodynamics and Enzyme Kinetics Have Led to Erroneous Conclusions Regarding the Metabolic Importance of Lactate Dehydrogenase Isoenzyme Expression
Misconceptions Regarding Basic Thermodynamics and Enzyme Kinetics Have Led to Erroneous Conclusions Regarding the Metabolic Importance of Lactate Dehydrogenase Isoenzyme Expression
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DOI：
10.1002/jnr.23994
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发表时间：
2017-11-01
影响因子：
4.2
通讯作者：
Schousboe, Arne
中科院分区：
文献类型：
--
作者：
Bak, Lasse K.;Schousboe, Arne
乳酸脱氢酶（LDH）催化丙酮酸和乳酸的相互转化，涉及辅酶NAD（+）。在脑激活过程中乳酸从星形胶质细胞穿梭到神经元的部分基础是两种细胞类型之间LDH同工酶的差异分布。在这篇简短的综述中，我们概述了神经元和星形胶质细胞中表达的LDH同工酶的基本动力学特性，并认为LDH同工酶的分布不以任何方式支配两个细胞室之间的乳酸定向流动。两个要点如下。首先，根据化学催化的一般概念，酶不影响化学反应的热力学平衡，而只是影响达到平衡的速度。因此，具有不同动力学参数的LDH同工酶的差异分布不能预测哪些细胞正在产生乳酸，哪些细胞正在消耗乳酸。第二，反应的热力学平衡是朝向还原的底物（即，乳酸盐），这反映在脑组织中测量的浓度中，表明反应在稳态下接近平衡。总之，LDH同工酶的细胞分布在确定神经元和星形胶质细胞之间的乳酸的任何定向流动方面几乎没有影响。(C)2017 Wiley Periodicals，Inc.
Lactate dehydrogenase (LDH) catalyzes the interconversion of pyruvate and lactate involving the coenzyme NAD(+). Part of the foundation for the proposed shuttling of lactate from astrocytes to neurons during brain activation is the differential distribution of LDH isoenzymes between the two cell types. In this short review, we outline the basic kinetic properties of the LDH isoenzymes expressed in neurons and astrocytes, and argue that the distribution of LDH isoenzymes does not in any way govern directional flow of lactate between the two cellular compartments. The two main points are as follows. First, in line with the general concept of chemical catalysis, enzymes do not influence the thermodynamic equilibrium of a chemical reaction but merely the speed at which equilibrium is obtained. Thus, differential distribution of LDH isoenzymes with different kinetic parameters does not predict which cells are producing and which are consuming lactate. Second, the thermodynamic equilibrium of the reaction is toward the reduced substrate (i.e., lactate), which is reflected in the concentrations measured in brain tissue, suggesting that the reaction is at near-equilibrium at steady state. To conclude, the cellular distribution of LDH isoenzymes is of little if any consequence in determining any directional flow of lactate between neurons and astrocytes. (C) 2017 Wiley Periodicals, Inc.