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Record Information
Version3.6
Creation Date2005-11-16 15:48:42 UTC
Update Date2016-02-11 01:02:07 UTC
HMDB IDHMDB00156
Secondary Accession NumbersNone
Metabolite Identification
Common NameL-Malic acid
DescriptionMalic acid is a tart-tasting organic dicarboxylic acid that plays a role in many sour or tart foods. Apples contain malic acid, which contributes to the sourness of a green apple. Malic acid can make a wine taste tart, although the amount decreases with increasing fruit ripeness. (wikipedia). In its ionized form malic acid is called malate. Malate is an intermediate of the TCA cycle along with fumarate. It can also be formed from pyruvate as one of the anaplerotic reactions. In humans, malic acid is both derived from food sources and synthesized in the body through the citric acid cycle or Krebs cycle which takes place in the mitochondria. Malate's importance to the production of energy in the body during both aerobic and anaerobic conditions is well established. Under aerobic conditions, the oxidation of malate to oxaloacetate provides reducing equivalents to the mitochondria through the malate-aspartate redox shuttle. During anaerobic conditions, where a buildup of excess of reducing equivalents inhibits glycolysis, malic acid's simultaneous reduction to succinate and oxidation to oxaloacetate is capable of removing the accumulating reducing equivalents. This allows malic acid to reverse hypoxia's inhibition of glycolysis and energy production. In studies on rats it has been found that only tissue malate is depleted following exhaustive physical activity. Other key metabolites from the citric acid cycle needed for energy production were found to be unchanged. Because of this, a deficiency of malic acid has been hypothesized to be a major cause of physical exhaustion. Notably, the administration of malic acid to rats has been shown to elevate mitochondrial malate and increase mitochondrial respiration and energy production.
Structure
Thumb
Synonyms
ValueSource
(-)-L-Malic acidChEBI
(S)-(-)-Hydroxysuccinic acidChEBI
L-2-Hydroxybutanedioic acidChEBI
L-Apple acidChEBI
L-Malic acidChEBI
MalateChEBI
Malic acidChEBI
S-2-Hydroxybutanedioic acidChEBI
(-)-L-MalateGenerator
(S)-MalateGenerator
(S)-(-)-HydroxysuccinateGenerator
L-2-HydroxybutanedioateGenerator
L-MalateGenerator
S-2-HydroxybutanedioateGenerator
(-)-(S)-MalateHMDB
(-)-(S)-Malic acidHMDB
(-)-HydroxysuccinateHMDB
(-)-Hydroxysuccinic acidHMDB
(-)-Malic acidHMDB
(2S)-2-HydroxybutanedioateHMDB
(2S)-2-Hydroxybutanedioic acidHMDB
(S)-Hydroxy-butanedioateHMDB
(S)-Hydroxy-butanedioic acidHMDB
(S)-HydroxybutanedioateHMDB
(S)-Hydroxybutanedioic acidHMDB
Apple acidHMDB
L-(-)-Malic acidHMDB
L-HydroxybutanedioateHMDB
L-Hydroxybutanedioic acidHMDB
L-HydroxysuccinateHMDB
L-Hydroxysuccinic acidHMDB
S-(-)-MalateHMDB
S-(-)-Malic acidHMDB
Chemical FormulaC4H6O5
Average Molecular Weight134.0874
Monoisotopic Molecular Weight134.021523302
IUPAC Name(2S)-2-hydroxybutanedioic acid
Traditional Name(-)-malic acid
CAS Registry Number97-67-6
SMILES
O[C@@H](CC(O)=O)C(O)=O
InChI Identifier
InChI=1S/C4H6O5/c5-2(4(8)9)1-3(6)7/h2,5H,1H2,(H,6,7)(H,8,9)/t2-/m0/s1
InChI KeyInChIKey=BJEPYKJPYRNKOW-REOHCLBHSA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as hydroxy fatty acids. These are fatty acids in which the chain bears a hydroxyl group.
KingdomOrganic compounds
Super ClassLipids and lipid-like molecules
ClassFatty Acyls
Sub ClassFatty acids and conjugates
Direct ParentHydroxy fatty acids
Alternative Parents
Substituents
  • Hydroxy fatty acid
  • Short-chain hydroxy acid
  • Beta-hydroxy acid
  • Hydroxy acid
  • Dicarboxylic acid or derivatives
  • Alpha-hydroxy acid
  • Secondary alcohol
  • Carboxylic acid
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organooxygen compound
  • Carbonyl group
  • Alcohol
  • Aliphatic acyclic compound
Molecular FrameworkAliphatic acyclic compounds
External Descriptors
Ontology
StatusDetected and Quantified
Origin
  • Endogenous
Biofunction
  • Component of Glyoxylate and dicarboxylate metabolism
  • Component of Pyruvate metabolism
ApplicationNot Available
Cellular locations
  • Cytoplasm
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point107 °CNot Available
Boiling PointNot AvailableNot Available
Water SolubilityNot AvailableNot Available
LogPNot AvailableNot Available
Predicted Properties
PropertyValueSource
Water Solubility218.0 mg/mLALOGPS
logP-0.87ALOGPS
logP-1.1ChemAxon
logS0.21ALOGPS
pKa (Strongest Acidic)3.2ChemAxon
pKa (Strongest Basic)-3.9ChemAxon
Physiological Charge-2ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area94.83 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity24.88 m3·mol-1ChemAxon
Polarizability10.93 Å3ChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
GC-MSGC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (3 TMS)splash10-000t-0940000000-142d6f5fc2efbf0d5109View in MoNA
GC-MSGC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (3 TMS)splash10-0002-0920000000-505483ce10ee3c4c9d20View in MoNA
GC-MSGC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (3 TMS)splash10-00di-9710000000-8f263d045d715ae9fe2bView in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)splash10-000i-9300000000-acd7d0159b8bb70b80fdView in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)splash10-0096-9000000000-7359292556d9d393d8f4View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)splash10-0097-9000000000-a111335688b3219c1fc1View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Negativesplash10-00lr-0942120000-9504700a82dcf5dc3adbView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Negativesplash10-0a4i-0900000000-45e58d8a75d957cc5c41View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Negativesplash10-03di-0900000000-4ec56105367de7bf0027View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 10V, Negativesplash10-001i-0900000000-1decf12f117200e0f28dView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 20V, Negativesplash10-03di-4900000000-86fd329658581c81c0ecView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 30V, Negativesplash10-00di-9100000000-82ffef2aa053f77cdbc5View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 40V, Negativesplash10-00di-9000000000-424bd54bc81a9db65a55View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 50V, Negativesplash10-0006-9000000000-a916941735427ee3c48dView in MoNA
1D NMR1H NMR SpectrumNot Available
1D NMR13C NMR SpectrumNot Available
2D NMR[1H,1H] 2D NMR SpectrumNot Available
2D NMR[1H,13C] 2D NMR SpectrumNot Available
Biological Properties
Cellular Locations
  • Cytoplasm
Biofluid Locations
  • Blood
  • Cellular Cytoplasm
  • Cerebrospinal Fluid (CSF)
  • Feces
  • Saliva
  • Urine
Tissue Location
  • Prostate
Pathways
NameSMPDB LinkKEGG Link
2-ketoglutarate dehydrogenase complex deficiencySMP00549Not Available
Citric Acid CycleSMP00057map00020
Congenital lactic acidosisSMP00546Not Available
Fumarase deficiencySMP00547Not Available
Glutaminolysis and CancerSMP02298Not Available
Leigh SyndromeSMP00196Not Available
Mitochondrial complex II deficiencySMP00548Not Available
Primary hyperoxaluria II, PH2SMP00558Not Available
Pyruvate Decarboxylase E1 Component Deficiency (PDHE1 Deficiency)SMP00334Not Available
Pyruvate Dehydrogenase Complex DeficiencySMP00212Not Available
Pyruvate dehydrogenase deficiency (E2)SMP00551Not Available
Pyruvate dehydrogenase deficiency (E3)SMP00550Not Available
Pyruvate kinase deficiencySMP00559Not Available
Pyruvate MetabolismSMP00060map00620
The oncogenic action of 2-hydroxyglutarateSMP02291Not Available
The oncogenic action of D-2-hydroxyglutarate in Hydroxygluaricaciduria SMP02359Not Available
The oncogenic action of FumarateSMP02295Not Available
The oncogenic action of L-2-hydroxyglutarate in HydroxygluaricaciduriaSMP02358Not Available
The oncogenic action of SuccinateSMP02292Not Available
Transfer of Acetyl Groups into MitochondriaSMP00466Not Available
Warburg EffectSMP00654Not Available
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified12.0 (0.0-21.0) uMAdult (>18 years old)BothNormal details
BloodDetected and Quantified3.2 +/- 0.9 uMAdult (>18 years old)BothNormal
    • Geigy Scientific ...
details
Cellular CytoplasmDetected and Quantified3200 (2800-3600) uMAdult (>18 years old)BothNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified3.0 +/- 3.0 uMAdult (>18 years old)BothNormal details
FecesDetected but not QuantifiedNot ApplicableAdult (>18 years old)Both
Normal
details
SalivaDetected but not QuantifiedNot ApplicableAdult (>18 years old)Male
Normal
details
SalivaDetected but not QuantifiedNot ApplicableAdult (>18 years old)Male
Normal
details
SalivaDetected but not QuantifiedNot ApplicableAdult (>18 years old)Male
Normal
details
SalivaDetected but not QuantifiedNot ApplicableAdult (>18 years old)Male
Normal
details
SalivaDetected but not QuantifiedNot ApplicableAdult (>18 years old)Male
Normal
details
SalivaDetected but not QuantifiedNot ApplicableAdult (>18 years old)Male
Normal
details
SalivaDetected but not QuantifiedNot ApplicableAdult (>18 years old)Male
Normal
details
SalivaDetected but not QuantifiedNot ApplicableAdult (>18 years old)Male
Normal
details
SalivaDetected but not QuantifiedNot ApplicableAdult (>18 years old)Male
Normal
details
SalivaDetected but not QuantifiedNot ApplicableAdult (>18 years old)Male
Normal
details
SalivaDetected and Quantified6.45 +/- 2.84 uMAdult (>18 years old)BothNormal
    • Zerihun T. Dame, ...
details
SalivaDetected and Quantified20.45 +/- 10.87 uMAdult (>18 years old)FemaleNormal details
UrineDetected and Quantified18.669 umol/mmol creatinineChildren (1 - 13 years old)Not Specified
Normal
    • Mordechai, Hien, ...
details
UrineDetected and Quantified2.63 umol/mmol creatinineAdult (>18 years old)BothNormal
    • Geigy Scientific ...
details
UrineDetected and Quantified2.0 (0.7-5.3) umol/mmol creatinineAdult (>18 years old)BothNormal details
UrineDetected and Quantified0.46 +/- 0.79 umol/mmol creatinineInfant (0-1 year old)BothNormal details
UrineDetected and Quantified0.5 umol/mmol creatinineAdult (>18 years old)BothNormal details
UrineDetected and Quantified116.959 +/- 45.313 umol/mmol creatinineChildren (1 - 13 years old)Not Specified
Normal
    • Mordechai, Hien, ...
details
UrineDetected and Quantified36.1(12.4-121.6) umol/mmol creatinineNewborn (0-30 days old)BothNormal details
UrineDetected and Quantified38.9 (25.5-93.0) umol/mmol creatinineInfant (0-1 year old)BothNormal details
UrineDetected and Quantified9.0 (2.2-19.0) umol/mmol creatinineChildren (1-13 years old)BothNormal details
UrineDetected and Quantified8.3 (2.8-30.1) umol/mmol creatinineAdolescent (13-18 years old)BothNormal details
Abnormal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
Cellular CytoplasmDetected and Quantified480 (470-490) uMAdult (>18 years old)BothAnoxia details
SalivaDetected and Quantified22.27 +/- 14.67 uMAdult (>18 years old)MaleAlzheimer's disease details
SalivaDetected and Quantified18.70 +/- 15.26 uMAdult (>18 years old)MaleFrontotemporal lobe dementia details
SalivaDetected and Quantified24.13 +/- 19.54 uMAdult (>18 years old)BothLewy body disease details
UrineDetected and Quantified33.616 +/- 24.099 umol/mmol creatinineChildren (1 - 13 years old)Not Specified
Eosinophilic esophagitis
    • Mordechai, Hien, ...
details
UrineDetected and Quantified65.119 +/- 40.319 umol/mmol creatinineChildren (1 - 13 years old)Not Specified
Eosinophilic esophagitis
    • Mordechai, Hien, ...
details
UrineDetected and Quantified187.187 +/- 183.405 umol/mmol creatinineChildren (1 - 13 years old)Not Specified
Gastroesophageal reflux disease
    • Mordechai, Hien, ...
details
Associated Disorders and Diseases
Disease References
Anoxia
  1. Zupke C, Sinskey AJ, Stephanopoulos G: Intracellular flux analysis applied to the effect of dissolved oxygen on hybridomas. Appl Microbiol Biotechnol. 1995 Dec;44(1-2):27-36. [8579834 ]
Associated OMIM IDsNone
DrugBank IDNot Available
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDFDB001044
KNApSAcK IDC00001192
Chemspider ID193317
KEGG Compound IDC00149
BioCyc IDNot Available
BiGG ID34045
Wikipedia LinkApple acid
NuGOwiki LinkHMDB00156
Metagene LinkHMDB00156
METLIN IDNot Available
PubChem Compound222656
PDB IDLMR
ChEBI ID30797
References
Synthesis ReferenceMcKenzie, Alex.; Plenderleith, H. J.; Walker, Nellie. Optical activation of racemic acid by d-malic acid. Journal of the Chemical Society, Transactions (1923), 123 2875-80.
Material Safety Data Sheet (MSDS)Download (PDF)
General References
  1. Sreekumar A, Poisson LM, Rajendiran TM, Khan AP, Cao Q, Yu J, Laxman B, Mehra R, Lonigro RJ, Li Y, Nyati MK, Ahsan A, Kalyana-Sundaram S, Han B, Cao X, Byun J, Omenn GS, Ghosh D, Pennathur S, Alexander DC, Berger A, Shuster JR, Wei JT, Varambally S, Beecher C, Chinnaiyan AM: Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression. Nature. 2009 Feb 12;457(7231):910-4. [19212411 ]
  2. Shoemaker JD, Elliott WH: Automated screening of urine samples for carbohydrates, organic and amino acids after treatment with urease. J Chromatogr. 1991 Jan 2;562(1-2):125-38. [2026685 ]
  3. Zupke C, Sinskey AJ, Stephanopoulos G: Intracellular flux analysis applied to the effect of dissolved oxygen on hybridomas. Appl Microbiol Biotechnol. 1995 Dec;44(1-2):27-36. [8579834 ]
  4. Fang TJ, Dalmasso JP: Antimicrobial activity of sulfur dioxide to certain lactic acid bacteria isolated from wines. Zhonghua Min Guo Wei Sheng Wu Ji Mian Yi Xue Za Zhi. 1993 Aug;26(3):116-31. [7982367 ]
  5. Splittstoesser DF, McLellan MR, Churey JJ: Heat resistance of Escherichia coli O157:H7 in apple juice. J Food Prot. 1996 Mar;59(3):226-9. [10463437 ]
  6. Denayrolles M, Aigle M, Lonvaud-Funel A: Cloning and sequence analysis of the gene encoding Lactococcus lactis malolactic enzyme: relationships with malic enzymes. FEMS Microbiol Lett. 1994 Feb 1;116(1):79-86. [8132158 ]

Enzymes

General function:
Involved in oxidoreductase activity
Specific function:
Not Available
Gene Name:
ME1
Uniprot ID:
P48163
Molecular weight:
64149.075
Reactions
L-Malic acid + NADP → Pyruvic acid + CO(2) + NADPHdetails
L-Malic acid + NADP → Pyruvic acid + Carbon dioxide + NADPH + Hydrogen Iondetails
General function:
Involved in oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor
Specific function:
Not Available
Gene Name:
MDH2
Uniprot ID:
P40926
Molecular weight:
35502.935
Reactions
L-Malic acid + NAD → Oxalacetic acid + NADHdetails
L-Malic acid + NAD → Oxalacetic acid + NADH + Hydrogen Iondetails
General function:
Involved in oxidoreductase activity
Specific function:
Not Available
Gene Name:
ME3
Uniprot ID:
Q16798
Molecular weight:
67067.875
Reactions
L-Malic acid + NADP → Pyruvic acid + CO(2) + NADPHdetails
L-Malic acid + NADP → Pyruvic acid + Carbon dioxide + NADPH + Hydrogen Iondetails
General function:
Involved in oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor
Specific function:
Not Available
Gene Name:
MDH1
Uniprot ID:
P40925
Molecular weight:
38627.255
Reactions
L-Malic acid + NAD → Oxalacetic acid + NADHdetails
L-Malic acid + NAD → Oxalacetic acid + NADH + Hydrogen Iondetails
General function:
Involved in fumarate hydratase activity
Specific function:
Also acts as a tumor suppressor.
Gene Name:
FH
Uniprot ID:
P07954
Molecular weight:
54636.585
Reactions
L-Malic acid → Fumaric acid + Waterdetails
General function:
Involved in oxidoreductase activity
Specific function:
Not Available
Gene Name:
ME2
Uniprot ID:
P23368
Molecular weight:
53585.73
Reactions
L-Malic acid + NAD → Pyruvic acid + CO(2) + NADHdetails
L-Malic acid + NAD → Pyruvic acid + Carbon dioxide + NADH + Hydrogen Iondetails
General function:
Involved in fumarate hydratase activity
Specific function:
Not Available
Gene Name:
FH
Uniprot ID:
B1ANK7
Molecular weight:
54636.6