Malic enzyme 1 (ME1)

Malic enzyme 1 (ME1) is a cytosolic, NADP-dependent oxidoreductase that catalyzes the conversion of malate to pyruvate, simultaneously generating NADPH from NADP+. ME1 is a key regulator of intermediary metabolism, bridging glycolytic and citric acid pathways and fueling anabolic processes such as fatty acid and cholesterol biosynthesis via its production of NADPH. It plays a central role in maintaining cellular redox homeostasis and is transcriptionally regulated by insulin and thyroxine. ME1 is functionally implicated in the biology of various cancers—contributing to proliferation, epithelial-mesenchymal transition, and chemoresistance—and is increasingly considered a promising therapeutic target. Aberrant expression or activity of ME1 has been linked to cancer development, diabetes, obesity, and metabolic syndrome. The enzyme can be inhibited by small molecules such as AS1134900, which bind allosterically and disrupt its enzymatic activity. Targeting ME1 may carry metabolic risks due to its fundamental role in NADPH generation and lipid metabolism.

Other names

NADP-dependent malic enzymeNADP-MEMalate dehydrogenase (oxaloacetate-decarboxylating) (NADP(+))HUMNDMEMESMalic enzyme, cytoplasmicMalic enzyme 1, cytosolicMalic enzyme 1, solublePyruvic-malic carboxylase

AS1134900 binds outside the active site, leading to allosteric inhibition of NADP-dependent malate conversion. This disrupts NADPH production. The inhibition is uncompetitive, requiring substrates NADP+ and malate for inhibitor binding.