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MetaCyc Compound: (S)-malate

Synonyms: (S)-malic acid, L-apple acid, L-malic acid, L-hydroxysuccinic acid, L-hydroxybutanedioic acid, L-malate

Superclasses: an acid all carboxy acids a carboxylate a dicarboxylate a C4-dicarboxylate (RS)-malate

Chemical Formula: C4H4O5

Molecular Weight: 132.07 Daltons

Monoisotopic Molecular Weight: 134.0215233031 Daltons

(<i>S</i>)-malate compound structure

SMILES: C(=O)([O-])CC(O)C([O-])=O

InChI: InChI=1S/C4H6O5/c5-2(4(8)9)1-3(6)7/h2,5H,1H2,(H,6,7)(H,8,9)/p-2/t2-/m0/s1

InChIKey: InChIKey=BJEPYKJPYRNKOW-REOHCLBHSA-L

Unification Links: CAS:97-67-6 , CAS:6915-15-7 , ChEBI:15589 , ChemSpider:4573566 , HMDB:HMDB00156 , IAF1260:34045 , KEGG:C00149 , MetaboLights:MTBLC15589 , PubChem:5459792

Standard Gibbs Free Energy of Change Formation (ΔfG in kcal/mol): -161.16376 Inferred by computational analysis [Latendresse13]

Reactions known to consume the compound:

anaerobic energy metabolism (invertebrates, mitochondrial) , C4 photosynthetic carbon assimilation cycle, NAD-ME type , chitin degradation to ethanol , L-carnitine degradation III :
(S)-malate + NAD+ → pyruvate + CO2 + NADH

bacillithiol biosynthesis :
UDP-N-acetyl-α-D-glucosamine + (S)-malate → malyl-N-acetyl-D-glucosamine + UDP + H+

C4 photosynthetic carbon assimilation cycle, NADP-ME type , C4 photosynthetic carbon assimilation cycle, PEPCK type :
(S)-malate + NADP+ → CO2 + pyruvate + NADPH

gluconeogenesis I :
(S)-malate + NAD+ → pyruvate + CO2 + NADH
(S)-malate + NADP+ → CO2 + pyruvate + NADPH

phaselate biosynthesis :
caffeoyl-CoA + (S)-malate → phaselate + coenzyme A

sinapate ester biosynthesis :
(S)-malate + 1-O-sinapoyl-β-D-glucose → sinapoyl-(S)-malate + β-D-glucopyranose

TCA cycle I (prokaryotic) , TCA cycle VII (acetate-producers) :
(S)-malate + an electron-transfer quinone[inner membrane] → oxaloacetate + an electron-transfer quinol[inner membrane]

TCA cycle VIII (helicobacter) :
(S)-malate + a menaquinone → oxaloacetate + a menaquinol

methyl ketone biosynthesis :
a carboxylate + ATP + coenzyme A → an acyl-CoA + AMP + diphosphate

Not in pathways:
an acyl-protein synthetase + a carboxylate + ATP → an acyl-protein thioester + AMP + diphosphate
a carboxylate + GTP + coenzyme A → an acyl-CoA + GDP + phosphate

Reactions known to produce the compound:

C4 photosynthetic carbon assimilation cycle, NADP-ME type , C4 photosynthetic carbon assimilation cycle, PEPCK type :
(S)-malate + NADP+ ← oxaloacetate + NADPH + H+

chitin degradation to ethanol , glycolate and glyoxylate degradation II , glyoxylate cycle , L-arabinose degradation IV , methylaspartate cycle , TCA cycle IV (2-oxoglutarate decarboxylase) , TCA cycle V (2-oxoglutarate:ferredoxin oxidoreductase) , xylose degradation IV :
acetyl-CoA + glyoxylate + H2O → (S)-malate + coenzyme A + H+

L-carnitine degradation III :
L-malic semialdehyde + NAD(P)+ + H2O → (S)-malate + NAD(P)H + 2 H+

Not in pathways:
(S)-malyl-CoA + H2O → (S)-malate + coenzyme A + H+

3,3'-thiodipropanoate degradation :
3-sulfinopropionate + an acyl-CoA → 3-sulfinopropanoyl-CoA + a carboxylate

dimethylsulfoniopropanoate degradation II (cleavage) :
dimethylsulfoniopropanoate + an acyl-CoA → dimethylsulfoniopropioyl-CoA + a carboxylate

NAD/NADP-NADH/NADPH mitochondrial interconversion (yeast) :
an aldehyde + NADP+ + H2O → a carboxylate + NADPH + 2 H+
an aldehyde + NAD+ + H2O → a carboxylate + NADH + 2 H+

phosphatidylcholine resynthesis via glycerophosphocholine :
a phosphatidylcholine + 2 H2O → sn-glycero-3-phosphocholine + 2 a carboxylate + 2 H+

Not in pathways:
a 1-acyl 2-lyso-phosphatidylcholine[periplasmic space] + H2O[periplasmic space]a carboxylate[periplasmic space] + sn-glycero-3-phosphocholine[periplasmic space] + H+[periplasmic space]
an acyl-CoA + H2O → a carboxylate + coenzyme A + H+
an L-1-phosphatidyl-inositol + H2O → a 1-acyl-sn-glycero-3-phospho-D-myo-inositol + a carboxylate + H+
a carboxylic ester + H2O → an alcohol + a carboxylate + H+
an aldehyde + oxygen + H2O → a carboxylate + hydrogen peroxide + H+
an aldehyde + FMNH2 + oxygen → hν + a carboxylate + FMN + H2O + 2 H+
an acylcholine + H2O → choline + a carboxylate + H+
a β-monogalactosyldiacylglycerol + 2 H2O → 2 a carboxylate + 3-β-D-galactosyl-sn-glycerol + 2 H+
an acyl phosphate + H2O → a carboxylate + phosphate + H+
an S-acylglutathione + H2O → a carboxylate + glutathione
an N-acyl-L-aspartate + H2O → L-aspartate + a carboxylate

Reactions known to both consume and produce the compound:

3-hydroxypropanoate cycle :
succinyl-CoA + (S)-malate ↔ succinate + (S)-malyl-CoA

anaerobic energy metabolism (invertebrates, cytosol) , C4 photosynthetic carbon assimilation cycle, NAD-ME type , gluconeogenesis I , gluconeogenesis III , glyoxylate cycle , L-aspartate degradation II :
(S)-malate + NAD+ ↔ oxaloacetate + NADH + H+

anaerobic energy metabolism (invertebrates, mitochondrial) , TCA cycle VII (acetate-producers) , TCA cycle VIII (helicobacter) :
(S)-malate ↔ fumarate + H2O

ethylmalonyl-CoA pathway :
(S)-malate + ATP + coenzyme A ↔ (S)-malyl-CoA + ADP + phosphate

formaldehyde assimilation I (serine pathway) :
(S)-malate + ATP + coenzyme A ↔ (S)-malyl-CoA + ADP + phosphate
(S)-malate + NAD+ ↔ oxaloacetate + NADH + H+

incomplete reductive TCA cycle :
(S)-malate + NAD+ ↔ oxaloacetate + NADH + H+
(S)-malate ↔ fumarate + H2O

methylaspartate cycle :
(S)-malate + NAD+ ↔ oxaloacetate + NADH + H+
(S)-malate ↔ fumarate + H2O

mixed acid fermentation :
(S)-malate + NAD+ ↔ oxaloacetate + NADH + H+
(S)-malate ↔ fumarate + H2O

pyruvate fermentation to propanoate I :
(S)-malate + NAD+ ↔ oxaloacetate + NADH + H+
(S)-malate ↔ fumarate + H2O

reductive TCA cycle I :
(S)-malate + NAD+ ↔ oxaloacetate + NADH + H+
(S)-malate ↔ fumarate + H2O

reductive TCA cycle II :
(S)-malate + NAD+ ↔ oxaloacetate + NADH + H+
(S)-malate ↔ fumarate + H2O

superpathway of glyoxylate cycle and fatty acid degradation :
(S)-malate + NAD+ ↔ oxaloacetate + NADH + H+
(S)-malate ↔ fumarate + H2O

TCA cycle I (prokaryotic) :
(S)-malate + NAD+ ↔ oxaloacetate + NADH + H+
(S)-malate ↔ fumarate + H2O

TCA cycle II (plants and fungi) :
(S)-malate + NAD+ ↔ oxaloacetate + NADH + H+
(S)-malate ↔ fumarate + H2O

TCA cycle III (animals) :
(S)-malate + NAD+ ↔ oxaloacetate + NADH + H+

In Reactions of unknown directionality:

Not in pathways:
(S)-lactate + oxaloacetate = pyruvate + (S)-malate

Not in pathways:
a monoamide of a dicarboxylate + H2O = a dicarboxylate + ammonium

Not in pathways:
eugenol + a carboxylate + NADP+ = a coniferyl ester + NADPH
a 2-acyl 1-lyso-phosphatidylcholine[periplasmic space] + H2O[periplasmic space] = a carboxylate[periplasmic space] + sn-glycero-3-phosphocholine[periplasmic space] + H+[periplasmic space]
an aldehyde + an electron-transfer quinone + H2O = a carboxylate + an electron-transfer quinol + H+
a triacyl-sn-glycerol + H2O = a 1,2-diacyl-sn-glycerol + a carboxylate + H+
a penicillin + H2O = 6-aminopenicillanate + a carboxylate
an aldehyde[periplasmic space] + FAD[periplasmic space] + H2O[periplasmic space] = a carboxylate[periplasmic space] + FADH2[periplasmic space]
a nitrile + 2 H2O = a carboxylate + ammonium
an aliphatic nitrile + 2 H2O = a carboxylate + ammonium
an N-acyl-L-homoserine lactone + H2O = L-homoserine lactone + a carboxylate
an aldehyde + an oxidized unknown electron acceptor + H2O = a carboxylate + an reduced unknown electron acceptor + H+
an N-acylated aromatic-L-amino acid + H2O = a carboxylate + an aromatic L-amino acid
an N-acylated-D-amino acid + H2O = a D-amino acid + a carboxylate
an N-acylated aliphatic-L-amino acid + H2O = a carboxylate + an aliphatic L-amino acid
a D-hexose + an acyl phosphate = a D-hexose-phosphate + a carboxylate
an aldehyde + 2 an oxidized ferredoxin + H2O = a carboxylate + 2 a reduced ferredoxin + 3 H+
an aldehyde + NAD(P)+ + H2O = a carboxylate + NAD(P)H + 2 H+
an N-acyl-D-glutamate + H2O = a carboxylate + D-glutamate
an anilide + H2O = aniline + a carboxylate + H+
a 5'-acylphosphoadenosine + H2O = a carboxylate + AMP + 2 H+
a 3-acylpyruvate + H2O = a carboxylate + pyruvate + H+
an N6acyl-L-lysine + H2O = a carboxylate + L-lysine
an N-acyl-D-aspartate + H2O = a carboxylate + D-aspartate

In Transport reactions:
(S)-malate[chloroplast stroma](S)-malate[cytosol] ,
(S)-malate[cytosol](S)-malate[mitochondrial lumen] ,
(S)-malate[periplasmic space] + 2 H+[periplasmic space](S)-malate[cytosol] + 2 H+[cytosol] ,
succinate[cytosol] + (S)-malate[periplasmic space](S)-malate[cytosol] + succinate[periplasmic space] ,
a C4-dicarboxylate[periplasmic space] + 2 H+[periplasmic space]a C4-dicarboxylate[cytosol] + 2 H+[cytosol] ,
a C4-dicarboxylate[periplasmic space] + 3 H+[periplasmic space]a C4-dicarboxylate[cytosol] + 3 H+[cytosol]

In Redox half-reactions:
oxaloacetate[in] + 2 H+[in] + 2 e-[membrane](S)-malate[in]

Enzymes activated by (S)-malate, sorted by the type of activation, are:

Activator (Mechanism unknown) of: isoflavone-7-O-glucoside-6''-O-malonate malonylesterase [Hinderer86] , isoflavone-7-O-glucoside-6''-O-malonate malonylesterase [Hinderer86] , isoflavone-7-O-glucoside-6''-O-malonate malonylesterase [Hinderer86] , isoflavone-7-O-glucoside-6''-O-malonate malonylesterase [Hinderer86] , isoflavone-7-O-glucoside-6''-O-malonate malonylesterase [Hinderer86]

Enzymes inhibited by (S)-malate, sorted by the type of inhibition, are:

Inhibitor (Competitive) of: 2-methyleneglutarate mutase [Kung71]

Inhibitor (Uncompetitive) of: malate dehydrogenase, NAD-requiring [Wang07b]

Inhibitor (Noncompetitive) of: glutamate dehydrogenase (NAD-dependent) [Bonete96, Comment 1]

Inhibitor (Allosteric) of: phosphoenolpyruvate carboxylase [Izui81] , phosphoenolpyruvate carboxylase , L-lactate dehydrogenase

Inhibitor (Mechanism unknown) of: glutamine synthetase adenylyltransferase [Ebner70] , malate synthase [Smith03] , isocitrate lyase [Honer99]

This compound has been characterized as an alternative substrate of the following enzymes: L-2-hydroxycarboxylate dehydrogenase (NAD+) , succinyl-CoA synthetase , (2R)-3-sulfolactate dehydrogenase , citramalate hydrolyase


References

Bonete96: Bonete MJ, Perez-Pomares F, Ferrer J, Camacho ML (1996). "NAD-glutamate dehydrogenase from Halobacterium halobium: inhibition and activation by TCA intermediates and amino acids." Biochim Biophys Acta 1996;1289(1);14-24. PMID: 8605224

Ebner70: Ebner E, Wolf D, Gancedo C, Elsasser S, Holzer H (1970). "ATP: glutamine synthetase adenylyltransferase from Escherichia coli B. Purification and properties." Eur J Biochem 1970;14(3);535-44. PMID: 4920894

Hinderer86: Hinderer W, Koster J, Barz W (1986). "Purfication and properties of a specific isoflavone 7-O-glucoside-6''-malonate malonyestrase from roots of chickpea (Cicer arietinum L.)." Arch Biochem Biophys 248(2);570-8. PMID: 3740841

Honer99: Honer Zu Bentrup K, Miczak A, Swenson DL, Russell DG (1999). "Characterization of activity and expression of isocitrate lyase in Mycobacterium avium and Mycobacterium tuberculosis." J Bacteriol 181(23);7161-7. PMID: 10572116

Izui81: Izui K, Taguchi M, Morikawa M, Katsuki H (1981). "Regulation of Escherichia coli phosphoenolpyruvate carboxylase by multiple effectors in vivo. II. Kinetic studies with a reaction system containing physiological concentrations of ligands." J Biochem 90(5);1321-31. PMID: 7040354

Kung71: Kung HF, Stadtman TC (1971). "Nicotinic acid metabolism. VI. Purification and properties of alpha-methyleneglutarate mutase (B 12-dependent) and methylitaconate isomerase." J Biol Chem 246(10);3378-88. PMID: 5574401

Latendresse13: Latendresse M. (2013). "Computing Gibbs Free Energy of Compounds and Reactions in MetaCyc."

Smith03: Smith CV, Huang CC, Miczak A, Russell DG, Sacchettini JC, Honer zu Bentrup K (2003). "Biochemical and structural studies of malate synthase from Mycobacterium tuberculosis." J Biol Chem 278(3);1735-43. PMID: 12393860

Wang07b: Wang J, Tan H, Zhao ZK (2007). "Over-expression, purification, and characterization of recombinant NAD-malic enzyme from Escherichia coli K12." Protein Expr Purif 53(1):97-103. PMID: 17215140


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Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
Page generated by SRI International Pathway Tools version 19.0 on Sun Aug 30, 2015, biocyc13.