Malate dehydrogenase 1 (MDH1)

Malate dehydrogenase 1 (MDH1) is the cytoplasmic isoform of malate dehydrogenase, a key enzyme in cellular metabolism. MDH1 catalyzes the reversible oxidation of malate to oxaloacetate using NAD+ as a cofactor, making it essential for the malate–aspartate shuttle that transfers reducing equivalents between cytosol and mitochondria. It plays roles beyond metabolism, including regulation of the p53 pathway under metabolic stress and modulation via post-translational modifications such as acetylation and methylation. Enhanced MDH1 activity supports NADPH generation and adipogenic differentiation; its dysregulation has been implicated in cancer and metabolic diseases. MDH1 shares a conserved structure among species, usually functioning as a homodimer featuring a Rossmann fold typical of NAD(P)-binding dehydrogenases. While not currently the target of approved therapies, it is under investigation as a potential anticancer target due to its central metabolic role and regulatory functions[1][2][3].

Other names

Malate dehydrogenase, cytoplasmicMDH1MDHAKARAromatic alpha-keto acid reductaseCytosolic malate dehydrogenaseDEE88EIEE88HEL-S-32MDH-sMGC:1375MOR2diiodophenylpyruvate reductaseepididymis secretory protein Li 32soluble malate dehydrogenase

Small-molecule inhibitors (planned or in research) act by blocking the catalytic activity of MDH1, potentially altering redox balance and metabolic flux in cancer cells[2].