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Intracellular dehydrogenases represent a broad class of enzymes responsible for catalyzing oxidation-reduction reactions by transferring electrons from a substrate to an electron acceptor, such as NAD+, NADP+, or FAD [1]. These enzymes are fundamental to cellular energy production and biosynthetic processes, playing pivotal roles in glycolysis, the citric acid cycle, and fatty acid oxidation [2]. In laboratory settings, the collective activity of these enzymes is often used as a proxy for cell viability and metabolic activity, as seen in tetrazolium-based assays like MTT or CCK-8 [3]. While the term refers to a functional group rather than a single protein, specific intracellular dehydrogenases have emerged as high-value therapeutic targets. For instance, mutations in isocitrate dehydrogenase 1 and 2 (IDH1/2) lead to the production of the oncometabolite 2-hydroxyglutarate, making them targets for precision oncology drugs like ivosidenib [4]. Targeting these enzymes allows for the modulation of specific metabolic vulnerabilities in diseased cells, although the ubiquity of many dehydrogenases across various tissues poses significant challenges for achieving therapeutic selectivity and minimizing systemic toxicity [5].
Inhibition of specific enzymatic activity to disrupt metabolic pathways, reduce the production of oncometabolites, or impair cellular redox balance.
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