ME3 tetramer decarboxylates MAL to PYR

Stable Identifier
Reaction [transition]
Homo sapiens
ME3:Mg2+ tetramer oxidatively decarboxylates MAL to PYR
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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).
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
33572903 The Pancreatic β-Cell: The Perfect Redox System

Jabůrek, M, Dlasková, A, Plecitá-Hlavatá, L, Tauber, J, Holendová, B, Ježek, P

Antioxidants (Basel) 2021
25594249 Mitochondrial malic enzyme 3 is important for insulin secretion in pancreatic β-cells

Stoker, SW, MacDonald, MJ, Kendrick, MA, Longacre, MJ, Hasan, NM

Mol. Endocrinol. 2015
7818469 Purification, cDNA cloning and heterologous expression of the human mitochondrial NADP(+)-dependent malic enzyme

Maurer-Fogy, I, Schwendenwein, R, Loeber, G

Biochem. J. 1994
36590518 Integrative structural and functional analysis of human malic enzyme 3: A potential therapeutic target for pancreatic cancer

Sharma, S, Gómez-Tamayo, JC, Mason, M, Yu, X, Shaffer, PL, Riley, D, Grell, TAJ, Wadia, J, Tresadern, G, Thompson, AA, Steele, R, Ortiz-Meoz, RF, Wagner, MV

Heliyon 2022
Catalyst Activity

malate dehydrogenase (decarboxylating) (NADP+) activity of ME3:Mg2+ tetramer [mitochondrial matrix]

Orthologous Events
Cross References
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