Cellular bioenergetics is an area showing promise for the development of new antimicrobials, antimalarials and cancer therapy. Enzymes involved in central carbon metabolism and energy generation are essential mediators of bacterial physiology, persistence and pathogenicity, lending themselves natural interest for drug discovery. In particular, succinate and malate are two major focal points in both the central carbon metabolism and the respiratory chain of Mycobacterium tuberculosis. Both serve as direct links between the citric acid cycle and the respiratory chain due to the quinone-linked reactions of succinate dehydrogenase, fumarate reductase and malate:quinone oxidoreductase. Inhibitors against these enzymes therefore hold the promise of disrupting two distinct, but essential, cellular processes at the same time. In this review, we discuss the roles and unique adaptations of these enzymes and critically evaluate the role that future inhibitors of these complexes could play in the bioenergetics target space.

细胞生物能学领域显示出有望开发新的抗微生物药，抗疟药和癌症疗法。参与中央碳代谢和能量产生的酶是细菌生理，持久性和致病性的重要介体，使它们自然而然地被药物发现所吸引。特别地，琥珀酸和苹果酸是结核分枝杆菌中心碳代谢和呼吸链的两个主要焦点。。由于琥珀酸脱氢酶，富马酸酯还原酶和苹果酸：醌氧化还原酶的醌连接反应，两者均充当柠檬酸循环和呼吸链之间的直接链接。因此，针对这些酶的抑制剂有望同时破坏两个不同但必不可少的细胞过程。在这篇综述中，我们讨论了这些酶的作用和独特的适应性，并严格评估了这些复合物的未来抑制剂可能在生物能学目标空间中发挥的作用。