Panov Alexander V, Mayorov Vladimir I, Dikalov Sergey I
Department of Biomedical Sciences, Mercer University School of Medicine, Macon, GA 31201, USA.
Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Int J Mol Sci. 2024 Nov 27;25(23):12740. doi: 10.3390/ijms252312740.
In recent decades, several discoveries have been made that force us to reconsider old ideas about mitochondria and energy metabolism in the light of these discoveries. In this review, we discuss metabolic interaction between various organs, the metabolic significance of the primary substrates and their metabolic pathways, namely aerobic glycolysis, lactate shuttling, and fatty acids β-oxidation. We rely on the new ideas about the supramolecular structure of the mitochondrial respiratory chain (respirasome), the necessity of supporting substrates for fatty acids β-oxidation, and the reverse electron transfer via succinate dehydrogenase during β-oxidation. We conclude that ATP production during fatty acid β-oxidation has its upper limits and thus cannot support high energy demands alone. Meanwhile, β-oxidation creates conditions that significantly accelerate the cycle: glucose-aerobic glycolysis-lactate-gluconeogenesis-glucose. Therefore, glycolytic ATP production becomes an important energy source in high energy demand. In addition, lactate serves as a mitochondrial substrate after converting to pyruvate + H by the mitochondrial lactate dehydrogenase. All coupled metabolic pathways are irreversible, and the enzymes are organized into multienzyme structures.
近几十年来,已有多项发现迫使我们根据这些发现重新审视关于线粒体和能量代谢的旧观念。在本综述中,我们讨论了各器官之间的代谢相互作用、主要底物的代谢意义及其代谢途径,即有氧糖酵解、乳酸穿梭和脂肪酸β氧化。我们依据关于线粒体呼吸链超分子结构(呼吸体)的新观念、脂肪酸β氧化对支持底物的必要性以及β氧化过程中通过琥珀酸脱氢酶的逆向电子传递。我们得出结论,脂肪酸β氧化过程中的ATP生成有其上限,因此无法单独满足高能量需求。同时,β氧化创造了显著加速以下循环的条件:葡萄糖 - 有氧糖酵解 - 乳酸 - 糖异生 - 葡萄糖。因此,糖酵解产生的ATP成为高能量需求时的重要能量来源。此外,乳酸在被线粒体乳酸脱氢酶转化为丙酮酸 + H后可作为线粒体底物。所有耦合的代谢途径都是不可逆的,且酶被组织成多酶结构。