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 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
33572903	The Pancreatic β-Cell: The Perfect Redox System Ježek, P, Holendová, B, Jabůrek, M, Tauber, J, Dlasková, A, Plecitá-Hlavatá, L	Antioxidants (Basel)	2021
25594249	Mitochondrial malic enzyme 3 is important for insulin secretion in pancreatic β-cells Hasan, NM, Longacre, MJ, Stoker, SW, Kendrick, MA, MacDonald, MJ	Mol. Endocrinol.	2015
7818469	Purification, cDNA cloning and heterologous expression of the human mitochondrial NADP(+)-dependent malic enzyme Loeber, G, Maurer-Fogy, I, Schwendenwein, R	Biochem. J.	1994
36590518	Integrative structural and functional analysis of human malic enzyme 3: A potential therapeutic target for pancreatic cancer Grell, TAJ, Mason, M, Thompson, AA, Gómez-Tamayo, JC, Riley, D, Wagner, MV, Steele, R, Ortiz-Meoz, RF, Wadia, J, Shaffer, PL, Tresadern, G, Sharma, S, Yu, X	Heliyon	2022