Malic enzyme 3, NADP(+)-dependent, mitochondrial (ME3)

Malic enzyme 3 (ME3) is a mitochondrial NADP(+)-dependent enzyme that catalyzes the oxidative decarboxylation of malate to pyruvate, generating NADPH in the process. ME3 plays key roles in energy metabolism, redox homeostasis, and supporting biosynthetic reactions by supplying reducing equivalents. Structurally, ME3 assembles into a tetramer and differs from its isoforms by being non-allosteric and having unique domain arrangements—a feature considered important for future drug development. Although not yet a target of approved drugs, ME3 has attracted attention as a therapeutic target in pancreatic cancer due to its role in cellular metabolic reprogramming; its structural characterization provides a basis for the rational design of selective inhibitors

Other names

Malic enzyme 3NADP-dependent malic enzyme, mitochondrialME3NADP-MEMalate dehydrogenase (oxaloacetate-decarboxylating) (NADP(+))Pyruvic-malic carboxylasemitochondrial NADP(+)-dependent malic enzyme 3

Hypothetical future mechanism: Small molecule inhibitors may bind non-allosteric sites, interfere with NADP(+) binding, or stabilize inactive conformations