ME1 tetramer decarboxylates MAL to PYR

Stable Identifier
Reaction [transition]
Homo sapiens
ME1:Mg2+ tetramer oxidatively decarboxylates MAL to PYR
Locations in the PathwayBrowser
SVG |   | PPTX  | SBGN
Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout
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).
Literature References
PubMed ID Title Journal Year
14596586 Structure and function of malic enzymes, a new class of oxidative decarboxylases

Tong, L, Chang, GG

Biochemistry 2003
23284632 Biophysical characterization of the dimer and tetramer interface interactions of the human cytosolic malic enzyme

Murugan, S, Hung, HC

PLoS ONE 2012
33064660 Malic enzyme 1 (ME1) in the biology of cancer: it is not just intermediary metabolism

Simmen, RCM, Alhallak, I, Simmen, FA

J Mol Endocrinol 2020
1935931 Malic enzyme in human liver. Intracellular distribution, purification and properties of cytosolic isozyme

Zelewski, M, SwierczyƄski, J

Eur. J. Biochem. 1991
24998673 Structural characteristics of the nonallosteric human cytosolic malic enzyme

Li, SY, Chen, HY, Hung, HC, Yang, PC, Hsieh, JY, Chen, MC, Chan, NL, Liu, JH

Biochim. Biophys. Acta 2014
7757881 Purification and properties of cytosolic and mitochondrial malic enzyme isolated from human brain

Bukato, G, Kochan, Z, SwierczyƄski, J

Int J Biochem Cell Biol 1995
Catalyst Activity

malate dehydrogenase (decarboxylating) (NADP+) activity of ME1 tetramer [cytosol]

This event is regulated
Negatively by
Orthologous Events
Cross References
Cite Us!