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在离体工作大鼠心脏中,乳酸和脂肪酸作为ATP来源的竞争关系。

Competition between lactate and fatty acids as sources of ATP in the isolated working rat heart.

作者信息

Schönekess B O

机构信息

Department of Pharmacology, The University of Alberta, Edmonton, Canada.

出版信息

J Mol Cell Cardiol. 1997 Oct;29(10):2725-33. doi: 10.1006/jmcc.1997.0504.

DOI:10.1006/jmcc.1997.0504
PMID:9344767
Abstract

Fatty acid oxidation is generally considered the major source of energy in the heart, although lactate oxidation can be a major contributor to ATP production, depending on the concentration and availability of other competing substrates. In this study, isolated working rat hearts were used to directly determine the relationship between lactate and fatty acid oxidation to overall ATP production from exogenous sources. A range of lactate from 0.5 to 8.0 mM lactate was added to hearts perfused with buffer containing 5.5 mM glucose, and either 0.4 or 1.2 mM palmitate over a 100 min period. Rates of glycolysis, glucose oxidation, lactate oxidation, and palmitate oxidation were determined. In the presence of 0.5 mM lactate and 0.4 mM palmitate, lactate oxidation provided 17% of the ATP production and palmitate oxidation provided 68%, with the remainder coming from glucose oxidation and glycolysis. In the presence of 0.4 mM palmitate, an increase in lactate from 0.5 to 8.0 mM increased the steady state rates of lactate oxidation from 1239+/-236 to 5247+/-940 nmol/min/g dry weight, respectively. The contribution of lactate oxidation to total ATP production increased to 37%, with palmitate oxidation now contributing only 52% of the total ATP produced. At 8.0 mM lactate and 1.2 mM palmitate, lactate oxidation contributed 13% of the total ATP production, while palmitate oxidation contributed 81%. This data demonstrates that under near physiological conditions of lactate (0.5 mM) and fatty acids (0.4 mM), the preferred energy substrate of the heart remains to be fatty acids, and that only at high levels of lactate, such as can be observed during exercise or severe stress, does lactate oxidation become a significant source of ATP production.

摘要

脂肪酸氧化通常被认为是心脏能量的主要来源,尽管乳酸氧化也可能是ATP产生的主要贡献者,这取决于其他竞争性底物的浓度和可利用性。在本研究中,使用离体工作大鼠心脏直接确定乳酸和脂肪酸氧化与外源底物产生的总ATP之间的关系。在100分钟内,将0.5至8.0 mM的一系列乳酸添加到灌注含5.5 mM葡萄糖以及0.4或1.2 mM棕榈酸酯缓冲液的心脏中。测定糖酵解、葡萄糖氧化、乳酸氧化和棕榈酸氧化的速率。在存在0.5 mM乳酸和0.4 mM棕榈酸酯的情况下,乳酸氧化提供了17%的ATP产生,棕榈酸氧化提供了68%,其余来自葡萄糖氧化和糖酵解。在存在0.4 mM棕榈酸酯的情况下,乳酸从0.5 mM增加到8.0 mM,使乳酸氧化的稳态速率分别从1239±236增加到5247±940 nmol/min/g干重。乳酸氧化对总ATP产生的贡献增加到37%,此时棕榈酸氧化仅占总ATP产生的52%。在8.0 mM乳酸和1.2 mM棕榈酸酯时,乳酸氧化占总ATP产生的13%,而棕榈酸氧化占81%。这些数据表明,在接近生理条件的乳酸(0.5 mM)和脂肪酸(0.4 mM)下,心脏的首选能量底物仍然是脂肪酸,只有在高浓度乳酸(如运动或严重应激期间可观察到的)时,乳酸氧化才会成为ATP产生的重要来源。

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