苹果酸脱氢酶
生物化学
柠檬酸循环
NAD+激酶
酶
生物
背景(考古学)
药物发现
辅因子
柠檬酸合酶
糖酵解
古生物学
作者
Charles S. Fermaintt,Sarah Wacker
出处
期刊:Essays in Biochemistry
[Portland Press]
日期:2024-05-31
被引量:1
摘要
Abstract Malate dehydrogenase (MDH) enzymes play critical roles in cellular metabolism, facilitating the reversible conversion of malate to oxaloacetate using NAD+/NADH as a cofactor. The two human isoforms of MDH have roles in the citric acid cycle and the malate-aspartate shuttle, and thus both are key enzymes in aerobic respiration as well as regenerating the pool of NAD+ used in glycolysis. This review highlights the potential of MDH as a therapeutic drug target in various diseases, including metabolic and neurological disorders, cancer, and infectious diseases. The most promising molecules for targeting MDH have been examined in the context of human malignancies, where MDH is frequently overexpressed. Recent studies have led to the identification of several antagonists, some of which are broad MDH inhibitors while others have selectivity for either of the two human MDH isoforms. Other promising compounds have been studied in the context of parasitic MDH, as inhibiting the function of the enzyme could selectively kill the parasite. Research is ongoing with these chemical scaffolds to develop more effective small-molecule drug leads that would have great potential for clinical applications.
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