Department of Biology, Suffolk University, Boston, MA U.S.A.
Department of Chemistry and Biochemistry, Providence College, Providence, RI, U.S.A.
Essays Biochem. 2024 Oct 3;68(2):53-55. doi: 10.1042/EBC20240044.
Malate dehydrogenases (MDHs) have been extensively studied since the 1960s due to their key roles in carbon metabolism and pathways such as redox balance and lipid synthesis. Recently, there has been renewed interest in these enzymes with the discovery of their role in the metabolic changes that occur during cancer and a widespread community of undergraduate teaching laboratories addressing MDH research questions, the Malate Dehydrogenase CUREs Community (MCC). This special issue describes different facets of MDH, including its physiological role, its structure-function relationships, its regulation through post-translational modifications, and perspectives on its evolutionary history. There are two human isoforms: a cytoplasmic isoform that carries out formation of NAD+ for glycolysis, and a mitochondrial isoform that plays a major role in the citric acid cycle. Although the sequences of these two isoforms vary, the structures of the enzymes are similar, and studies suggest that each isoform may form complexes with other enzymes in common pathways. Experimental and theoretical advances have helped to characterize the post-translational modifications of MDH, allowing us to ask more complex questions involving the regulation of the enzyme and substrate promiscuity in the context of cancer. Additionally, there are many unresolved questions on the role of malate dehydrogenase in other organisms, especially in parasites. The review articles in this issue seek to shed light on the latest advances in our understanding of MDH and highlight areas for future studies.
苹果酸脱氢酶（MDH）自 20 世纪 60 年代以来就因其在碳代谢和氧化还原平衡、脂质合成等途径中的关键作用而被广泛研究。最近，由于发现了这些酶在癌症发生过程中的代谢变化中的作用，以及广泛的本科教学实验室都在研究 MDH 相关问题，人们对这些酶重新产生了兴趣，成立了苹果酸脱氢酶治愈社区（MCC）。本期特刊描述了 MDH 的不同方面，包括其生理作用、结构-功能关系、通过翻译后修饰的调节以及其进化历史的观点。有两种人类同工酶：一种是在糖酵解过程中形成 NAD+的细胞质同工酶，另一种是在线粒体中发挥主要作用的柠檬酸循环同工酶。尽管这两种同工酶的序列不同，但酶的结构相似，研究表明，每种同工酶可能与共同途径中的其他酶形成复合物。实验和理论的进展有助于描述 MDH 的翻译后修饰，使我们能够提出更复杂的问题，涉及酶的调节和癌症背景下的底物简并性。此外，关于苹果酸脱氢酶在其他生物体中的作用，特别是在寄生虫中的作用，还有许多未解决的问题。本期特刊中的综述文章旨在阐明我们对 MDH 的最新理解，并强调未来研究的领域。
