Reactome | ME3 tetramer decarboxylates MAL to PYR

ME3 tetramer decarboxylates MAL to PYR

Stable Identifier

R-HSA-9012349

Type

Reaction [transition]

Species

Homo sapiens

Compartment

mitochondrial matrix

Synonyms

ME3:Mg2+ tetramer oxidatively decarboxylates MAL to PYR

ReviewStatus

5/5

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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