Reactome | ME1 tetramer decarboxylates MAL to PYR

ME1 tetramer decarboxylates MAL to PYR

Stable Identifier

R-HSA-9012036

Type

Reaction [transition]

Species

Homo sapiens

Compartment

cytosol

Synonyms

ME1:Mg2+ tetramer oxidatively decarboxylates MAL to PYR

ReviewStatus

5/5

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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 Chang, GG, Tong, L	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, FA, Alhallak, I, Simmen, RCM	J Mol Endocrinol	2020
1935931	Malic enzyme in human liver. Intracellular distribution, purification and properties of cytosolic isozyme Zelewski, M, Swierczyński, J	Eur. J. Biochem.	1991
24998673	Structural characteristics of the nonallosteric human cytosolic malic enzyme Hsieh, JY, Li, SY, Chen, MC, Yang, PC, Chen, HY, Chan, NL, Liu, JH, Hung, HC	Biochim. Biophys. Acta	2014
7757881	Purification and properties of cytosolic and mitochondrial malic enzyme isolated from human brain Bukato, G, Kochan, Z, Swierczyński, J	Int J Biochem Cell Biol	1995