Malic enzyme (ME (for isoforms: ME1, ME2, ME3))

Malic enzyme (ME) is a family of enzymes that catalyze the oxidative decarboxylation of L-malate to pyruvate, producing CO₂ and NAD(P)H in the presence of a divalent cation (Mg²⁺ or Mn²⁺)[1][9][10]. Three isoforms exist in mammals: cytosolic NADP-dependent malic enzyme (ME1), mitochondrial NAD(P)-dependent malic enzyme (ME2), and mitochondrial NADP-dependent malic enzyme (ME3)[2][10]. These enzymes are homotetrameric proteins, often described as dimers of dimers, each monomer comprised of four domains[1][2][7][10]. Malic enzymes are critical for generating NADPH for fatty acid synthesis, maintaining redox balance, and supporting biosynthetic and energy regulation processes[2][10]. Structural distinctions among isoforms underpin functional diversity and allosteric regulation, notably with an exo nucleotide-binding site and an allosteric site for inhibitors (ATP) and activators (fumarate)[1][5][7]. Malic enzymes are increasingly investigated as therapeutic targets, particularly in cancer, metabolic diseases, and disorders of redox imbalance, due to their essential metabolic roles[2][10]. Genetic variants and altered isoform expression can serve as biomarkers or modulate drug response[7][10].

Other names

Malate oxidoreductaseCytosolic NADP-dependent malic enzymeMitochondrial NAD(P)-dependent malic enzymeMitochondrial NADP-dependent malic enzyme

Inhibition of malic enzyme disrupts cellular metabolism and increases vulnerability of cancer cells under glucose restriction[2][10]