NADP-dependent malic enzyme (ME3, aka m-NADP-ME) is a mitochondrial enzyme that oxidatively decarboxylates (s)-malate (MAL) to pyruvate (PYR) and CO2 using NADP+ and Mg2+ as cofactors. ME3 forms a tetramer (Loeber et al., 1994; Grell et al., 2023). ME3 may play a role in insulin secretion, but how it does this in pancreatic beta cells has yet to be established (Hasan et al., 2015; reviewed in Jezek et al., 2021).
Malic enzymes (MEs) are a family of homotetrameric enzymes that catalyze the reversible oxidative decarboxylation of L-malate to pyruvate, with a simultaneous reduction of NAD(P)+ to NAD(P)H. As MEs generate NADPH and NADH, they may play roles in energy production and reductive biosynthesis. Humans possess three ME isoforms: ME1 is cytosolic and utilizes NADP+, ME3 is mitochondrial and can utilize NADP+, and ME2 is mitochondrial and can utilize either NAD+ or NADP+ (Chang & Tong, 2003; Murugan & Hung, 2012).
NADP-dependent malic enzyme (ME1, aka c-NADP-ME) is a cytosolic enzyme that oxidatively decarboxylates (S)-malate (MAL) to pyruvate (PYR) and CO2 using NADP+ as cofactor (Zelewski & Swierczynski, 1991). ME1 exists as a dimer of dimers (Murugan & Hung, 2012; Hsieh et al., 2014), and a divalent metal such as Mg2+ or Mn2+ is essential for catalysis (Bukato et al., 1995; Chang & Tong, 2003). In tumor cells, the reduction of ME1 gene expression or the inhibition of its activity resulted in decreases in proliferation, epithelial-to-mesenchymal transition, and in vitro migration, and conversely, in promotion of oxidative stress, apoptosis and cellular senescence (reviewed by Simmen et al., 2020).
Malic enzymes (MEs) are a family of homotetrameric enzymes that catalyze the reversible oxidative decarboxylation of L-malate to pyruvate, with a simultaneous reduction of NAD(P)+ to NAD(P)H. As MEs generate NADPH and NADH, they may play roles in energy production and reductive biosynthesis. Humans possess three ME isoforms: ME1 is cytosolic and utilizes NADP+, ME3 is mitochondrial and can utilize NADP+, and ME2 is mitochondrial and can utilize either NAD+ or NADP+ (Chang & Tong, 2003; Murugan & Hung, 2012).