ME1 tetramer decarboxylates MAL to PYR

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). <br/><br/>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依赖性苹果酸酶（ME1，又称c-NADP-ME）是一种细胞质酶，它能以NADP+为辅因子，将（S）-苹果酸（MAL）氧化脱羧生成丙酮酸（PYR）和二氧化碳（CO2）（参见Zelewski & Swierczynski，1991）。ME1以二聚体的二聚体形式存在（Murugan & Hung，2012；Hsieh等，2014），而如Mg2+或Mn2+等双价金属离子对于其催化活性至关重要（Bukato等，1995；Chang & Tong，2003）。在肿瘤细胞中，ME1基因表达的降低或其活性的抑制会导致细胞增殖、上皮间质转化和体外迁移能力的下降，反之，则会促进氧化应激、细胞凋亡和细胞衰老（Simmen等，2020年综述）。苹果酸酶（MEs）是一类同源四聚体酶家族，催化L-苹果酸的可逆性氧化脱羧生成丙酮酸，同时将NAD(P)+还原为NAD(P)H。由于苹果酸酶可生成NADPH和NADH，它们可能在能量生产和还原性生物合成中发挥重要作用。人类拥有三种ME同工酶：ME1为细胞质型，利用NADP+；ME3为线粒体型，可利用NADP+；ME2为线粒体型，可利用NAD+或NADP+（Chang & Tong，2003；Murugan & Hung，2012）。