Malic enzyme 1, cytosolic (ME1) (ME1)

Malic enzyme 1, cytosolic (ME1) is a key metabolic enzyme that catalyzes the reversible oxidative decarboxylation of L-malate to pyruvate, concurrently reducing NADP+ to NADPH [1, 5]. This reaction serves as a critical source of cytosolic NADPH, which is essential for fatty acid and cholesterol biosynthesis [1, 3]. Additionally, the NADPH produced by ME1 is vital for maintaining cellular redox homeostasis by supporting the glutathione and thioredoxin antioxidant systems [1, 5]. In many cancer types, such as pancreatic, breast, and gastrointestinal cancers, ME1 is frequently overexpressed and correlates with poor patient prognosis [5, 8]. It supports the malignant phenotype by providing the metabolic building blocks and antioxidant capacity required for rapid tumor growth and survival under stress [1, 9]. ME1 is also a target for synthetic lethality in tumors with malic enzyme 2 (ME2) deletions, which are common in pancreatic ductal adenocarcinoma [10, 12]. Experimental small-molecule inhibitors, such as AS1134900, have shown promise in selectively targeting ME1 to induce oxidative stress and inhibit tumor progression in preclinical models [10, 11]. Beyond oncology, ME1 is implicated in metabolic disorders like obesity and type 2 diabetes due to its regulatory role in lipogenesis [1, 3].

Other names

NADP-dependent malic enzyme, cytosolic [1, 5]Malate dehydrogenase (oxaloacetate-decarboxylating) (NADP+) [5, 6]Cytosolic malic enzyme [3]NADP-ME [1]

Allosteric inhibition of enzymatic activity to deplete cytosolic NADPH, increase reactive oxygen species (ROS), and disrupt fatty acid biosynthesis [10, 11].