Physiology of malate dehydrogenase and how dysregulation leads to disease

苹果酸脱氢酶 疾病 生理学 脱氢酶 生物 生物化学 医学 内科学
作者
Amy D. Parente,Danielle E. Bolland,Kathryn L. Huisinga,Joseph Provost
出处
期刊:Essays in Biochemistry [Portland Press]
卷期号:68 (2): 121-134 被引量:3
标识
DOI:10.1042/ebc20230085
摘要

Abstract 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.
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