苹果酸脱氢酶 (MDH) 在哺乳动物组织代谢中至关重要，参与其经典作用之外的各种途径，并强调其对细胞需求的适应性。这种酶参与维持氧化还原平衡、脂质合成和谷氨酰胺代谢，并支持快速增殖细胞的能量和生物合成需求。 MDH 参与谷氨酰胺代谢强调了其在细胞生理学中的重要性。相反，它对脂质代谢的贡献凸显了它在细胞维持和增殖所需的重要生物合成过程中的作用。该酶的调节机制（例如翻译后修饰）强调了其在代谢调节中的复杂性和重要性，使 MDH 成为代谢失调的潜在靶点。此外，MDH 与各种病理学（包括癌症和神经系统疾病）的关联表明它参与了疾病进展。 MDH 同工型 MDH1 和 MDH2 在乳腺癌、前列腺癌和胰腺导管腺癌等癌症中的过度表达以及结构修饰表明它们在肿瘤细胞的代谢适应中发挥着关键作用。此外，与嗜铬细胞瘤、副神经节瘤和其他代谢疾病相关的 MDH2 突变强调了 MDH 在代谢稳态中的作用。本综述重点关注 MDH 作为生物标志物和治疗靶点的潜力，提倡进一步研究其在健康和疾病中的多功能作用和调节机制。© 2024 作者。由波特兰出版社有限公司代表生化学会出版。

Malate dehydrogenase (MDH) is pivotal in mammalian tissue metabolism, participating in various pathways beyond its classical roles and highlighting its adaptability to cellular demands. This enzyme is involved in maintaining redox balance, lipid synthesis, and glutamine metabolism and supports rapidly proliferating cells' energetic and biosynthetic needs. The involvement of MDH in glutamine metabolism underlines its significance in cell physiology. In contrast, its contribution to lipid metabolism highlights its role in essential biosynthetic processes necessary for cell maintenance and proliferation. The enzyme's regulatory mechanisms, such as post-translational modifications, underscore its complexity and importance in metabolic regulation, positioning MDH as a potential target in metabolic dysregulation. Furthermore, the association of MDH with various pathologies, including cancer and neurological disorders, suggests its involvement in disease progression. The overexpression of MDH isoforms MDH1 and MDH2 in cancers like breast, prostate, and pancreatic ductal adenocarcinoma, alongside structural modifications, implies their critical role in the metabolic adaptation of tumor cells. Additionally, mutations in MDH2 linked to pheochromocytomas, paragangliomas, and other metabolic diseases emphasize MDH's role in metabolic homeostasis. This review spotlights MDH's potential as a biomarker and therapeutic target, advocating for further research into its multifunctional roles and regulatory mechanisms in health and disease.© 2024 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.