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Showing metabocard for (S)-lipoic acid (HMDB0014312)

IdentificationTaxonomyOntologyPhysical propertiesSpectraBiological propertiesConcentrationsLinksReferencesenzymes (5) Show 5 proteinsXML
enzymes (5) Show 5 proteins
Record Information
Version4.0
StatusExpected but not Quantified
Creation Date2012-09-06 15:16:49 UTC
Update Date2017-12-07 02:44:39 UTC
HMDB IDHMDB0014312
Secondary Accession Numbers
  • HMDB14312
Metabolite Identification
Common Name(S)-lipoic acid
DescriptionLipoic acid (LA), also known as ?-lipoic acid[2] and alpha lipoic acid (ALA)[3] is an organosulfur compound derived from octanoic acid. The carbon atom at C6 is chiral and the molecule exists as two enantiomers (R)-(+)-lipoic acid (RLA) and (S)-(-)-lipoic acid (SLA) and as a racemic mixture (R/S)-lipoic acid (R/S-LA). Only the (R)-(+)-enantiomer exists in nature and is an essential cofactor of four mitochondrial enzyme complexes. Endogenously synthesized RLA is essential for life and aerobic metabolism. The precursor to lipoic acid, octanoic acid, is made via fatty acid biosynthesis in the form of octanoyl-acyl carrier protein. In eukaryotes, a second fatty acid biosynthetic pathway in mitochondria is used for this purpose. The octanoate is transferred from a thioester of acyl carrier protein to an amide of the lipoyl domain by an octanoyltransferase. The sulfur centers are inserted into the 6th and 8th carbons of octanoate via a radical SAM mechanism, by lipoyl synthase. Lipoic acid can be removed whenever proteins are degraded and by action of the enzyme lipoamidase.[8] Free lipoate can be attached to the lipoyl domain by the enzyme lipoate protein ligase. The ligase activity of this enzyme requires ATP. Lipoate protein ligases proceed via an enzyme bound lipoyl adenylate intermediate. Both RLA and R/S-LA are available as over-the-counter nutritional supplements and have been used nutritionally and clinically since the 1950s for various diseases and conditions. It is often regarded as a vitamin-like antioxidant. Lipoic Acid is generally involved in oxidative decarboxylations of keto acids and is presented as a growth factor for some organisms. Some recent studies have suggested that the S-enantiomer in fact has an inhibiting effect on the R-enantiomer, reducing its biological activity substantially and actually adding to oxidative stress rather than reducing it. Furthermore, the S-enantiomer has been found to reduce the expression of GLUT-4s in cells, responsible for glucose uptake, and hence reduce insulin sensitivity.
Structure
Thumb
MOLSDF3D-SDFPDBSMILESInChI View 3D Structure
Synonyms
ValueSource
(+)-alpha-Lipoic acidChEBI
(R)-(+)-LipoateChEBI
(R)-(+)-Lipoic acidChEBI
(R)-1,2-Dithiolane-3-pentanoic acidChEBI
(R)-1,2-Dithiolane-3-valeric acidChEBI
(R)-6,8-Thioctic acidChEBI
alpha-Lipoic acidChEBI
Lipoic acidChEBI
R-(+)-Lipoic acidChEBI
R-LAChEBI
RLAChEBI
Thioctic acidChEBI
Thioctic acid D-formChEBI
(+)-a-LipoateGenerator
(+)-a-Lipoic acidGenerator
(+)-alpha-LipoateGenerator
(+)-α-lipoateGenerator
(+)-α-lipoic acidGenerator
(R)-LipoateGenerator
(R)-1,2-Dithiolane-3-pentanoateGenerator
(R)-1,2-Dithiolane-3-valerateGenerator
(R)-6,8-ThioctateGenerator
a-LipoateGenerator
a-Lipoic acidGenerator
alpha-LipoateGenerator
α-lipoateGenerator
α-lipoic acidGenerator
LipoateGenerator
R-(+)-LipoateGenerator
ThioctateGenerator
Thioctate D-formGenerator
Alpha Lippon alMeSH
Alpha-Lippon alMeSH
AlphaLippon alMeSH
AlphaflamMeSH
Hexal brand OF thioctic acidMeSH
Injekt, thiogammaMeSH
Liponsaure ratiopharmMeSH
Liponsaure-ratiopharmMeSH
Stadapharm brand OF thioctic acidMeSH
Thioctacide TMeSH
Verla liponMeSH
Viatris brand OF thioctic acidMeSH
alpha Liponaure heumannMeSH
alpha Liponsaure von CTMeSH
AlphaLiponsaure von CTMeSH
DuraliponMeSH
Ratiopharm brand OF thioctic acidMeSH
Aliud brand OF thioctic acidMeSH
Alpha-Liponsaure sofotecMeSH
AlphaLipon stadaMeSH
AzulipontMeSH
Heumann brand OF thioctic acidMeSH
Illa brand OF thioctic acidMeSH
Illa brand OF thioctic acid tromethamineMeSH
Juta brand OF thioctic acidMeSH
MTW AlphaliponsaureMeSH
Pleomix AlphaMeSH
PleomixAlphaMeSH
PleomixAlpha NMeSH
Q Pharm brand OF thioctic acidMeSH
Q-Pharm brand OF thioctic acidMeSH
Thiogamma injektMeSH
alpha VibolexMeSH
AlphaVibolexMeSH
biomo Brand OF thioctic acidMeSH
biomo-LiponMeSH
BiomoliponMeSH
CT-Arzneimittel brand OF thioctic acidMeSH
Acid, alpha-lipoicMeSH
Alpha LipogammaMeSH
Alpha Lipon stadaMeSH
Alpha-LipogammaMeSH
Alpha-Lipon stadaMeSH
AlphaLipogammaMeSH
AlphaLiponsaure sofotecMeSH
FenintMeSH
JuthiacMeSH
Merck dura brand OF thioctic acidMeSH
Pleomix Alpha NMeSH
Rosen brand OF thioctic acidMeSH
Thiogamma oralMeSH
TromliponMeSH
Trommsdorgg brand OF thioctic acidMeSH
Viatris brand OF thioctic acid tromethamineMeSH
Worwag brand OF thioctic acidMeSH
Worwag brand OF thioctic acid meglumineMeSH
alpha Lipoic acidMeSH
alpha-Liponsaure von CTMeSH
alpha-VibolexMeSH
AlphaLiponaure heumannMeSH
biomo LiponMeSH
CT Arzneimittel brand OF thioctic acidMeSH
Esparma brand OF thioctic acidMeSH
Alpha Liponsaure sofotecMeSH
Azupharma brand OF thioctic acidMeSH
Generosan brand OF thioctic acidMeSH
Lichtenstein brand OF thioctic acidMeSH
LiponsaureratiopharmMeSH
MTW Brand OF thioctic acidMeSH
MTW-AlphaliponsaureMeSH
MTWAlphaliponsaureMeSH
NeuriumMeSH
Pharmacia brand OF thioctic acidMeSH
Pleomix-AlphaMeSH
Pleomix-Alpha NMeSH
Sofotec brand OF thioctic acidMeSH
ThioctacidMeSH
Verla brand OF thioctic acidMeSH
Verla-liponMeSH
VerlaLiponMeSH
alpha-Liponaure heumannMeSH
Espa liponMeSH
Espa-liponMeSH
EspaliponMeSH
Chemical FormulaC8H14O2S2
Average Molecular Weight206.326
Monoisotopic Molecular Weight206.043521072
IUPAC Name5-[(3R)-1,2-dithiolan-3-yl]pentanoic acid
Traditional Namelipoic acid
CAS Registry Number1077-27-6
SMILES
OC(=O)CCCC[C@@H]1CCSS1
InChI Identifier
InChI=1S/C8H14O2S2/c9-8(10)4-2-1-3-7-5-6-11-12-7/h7H,1-6H2,(H,9,10)/t7-/m1/s1
InChI KeyAGBQKNBQESQNJD-SSDOTTSWSA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as lipoic acids and derivatives. These are compounds containing a lipoic acid moiety (or a derivative thereof), which consists of a pentanoic acid (or derivative) attached to the C3 carbon atom of a 1,2-dithiolane ring.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassDithiolanes
Sub ClassLipoic acids and derivatives
Direct ParentLipoic acids and derivatives
Alternative Parents
Substituents
  • Lipoic_acid_derivative
  • Medium-chain fatty acid
  • Heterocyclic fatty acid
  • Thia fatty acid
  • Fatty acyl
  • Fatty acid
  • 1,2-dithiolane
  • Organic disulfide
  • Monocarboxylic acid or derivatives
  • Carboxylic acid
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organic oxide
  • Organic oxygen compound
  • Carbonyl group
  • Aliphatic heteromonocyclic compound
Molecular FrameworkAliphatic heteromonocyclic compounds
External Descriptors
Ontology
Disposition

Biological location:

Process

Naturally occurring process:

Role

Biological role:

Industrial application:

Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water Solubility0.22 g/LNot Available
LogP2.1Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.22 g/LALOGPS
logP2.75ALOGPS
logP2.11ChemAxon
logS-3ALOGPS
pKa (Strongest Acidic)4.52ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area37.3 ŲChemAxon
Rotatable Bond Count5ChemAxon
Refractivity54.37 m³·mol⁻¹ChemAxon
Polarizability21.74 ųChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-0aba-3900000000-46fc1d57abcc26f6720eView in MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0ufu-5900000000-716655e029db4b97efd9View in MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positivesplash10-0hbi-6920000000-011fb15a0f9ca4513029View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)splash10-0a4r-0940000000-dead1b29e79e0002da2aView in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)splash10-0f8c-9200000000-b6035bdb4abd0d267297View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)splash10-0059-9000000000-62e73cabbac1531f5145View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0a4i-1920000000-2b265e3ed116fbc0a2eaView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0ab9-2910000000-9142e84d978f4a481551View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0a4i-9200000000-8bdfe1c35977a8c80985View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0a4r-0940000000-6cecd351951f396a3035View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-08gr-6910000000-f169816d57d2290b0d9eView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0m2c-9700000000-57ae386a681b98208a4bView in MoNA
1D NMR1H NMR SpectrumNot AvailableView in JSpectraViewer
2D NMR[1H,13C] 2D NMR SpectrumNot AvailableView in JSpectraViewer
Biological Properties
Cellular Locations
  • Cytoplasm
  • Membrane
Biospecimen Locations
  • Blood
  • Urine
Tissue LocationNot Available
Pathways
NameSMPDB/PathwhizKEGG
3-Phosphoglycerate dehydrogenase deficiencyThumbThumb?image type=greyscaleThumb?image type=simpleNot Available
Ammonia RecyclingThumbThumb?image type=greyscaleThumb?image type=simpleMap00910
Dihydropyrimidine Dehydrogenase Deficiency (DHPD)ThumbThumb?image type=greyscaleThumb?image type=simpleNot Available
Dimethylglycine Dehydrogenase DeficiencyThumbThumb?image type=greyscaleThumb?image type=simpleNot Available
Dimethylglycine Dehydrogenase DeficiencyThumbThumb?image type=greyscaleThumb?image type=simpleNot Available
Normal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB00166 details
UrineExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB00166 details
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDNot Available
Phenol Explorer Compound IDNot Available
FoodDB IDFDB022631
KNApSAcK IDC00000754
Chemspider ID5886
KEGG Compound IDC16241
BioCyc IDLIPOIC-ACID
BiGG ID35801
Wikipedia LinkLipoic_acid
METLIN ID126
PubChem Compound6112
PDB IDLPA
ChEBI ID30314
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General References
  1. Perham RN: Swinging arms and swinging domains in multifunctional enzymes: catalytic machines for multistep reactions. Annu Rev Biochem. 2000;69:961-1004. [PubMed:10966480 ]
  2. REED LJ, DeBUSK BG, GUNSALUS IC, HORNBERGER CS Jr: Crystalline alpha-lipoic acid; a catalytic agent associated with pyruvate dehydrogenase. Science. 1951 Jul 27;114(2952):93-4. [PubMed:14854913 ]

Enzymes

Enzyme Details
1. NADPH--cytochrome P450 reductase
General function:
Involved in oxidoreductase activity
Specific function:
This enzyme is required for electron transfer from NADP to cytochrome P450 in microsomes. It can also provide electron transfer to heme oxygenase and cytochrome B5.
Gene Name:
POR
Uniprot ID:
P16435
Molecular weight:
77047.575
References
  1. Dudka J: Decrease in NADPH-cytochrome P450 reductase activity of the human heart, Liver and lungs in the presence of alpha-lipoic acid. Ann Nutr Metab. 2006;50(2):121-5. Epub 2006 Jan 2. [PubMed:16391466 ]
  2. Wen B, Coe KJ, Rademacher P, Fitch WL, Monshouwer M, Nelson SD: Comparison of in vitro bioactivation of flutamide and its cyano analogue: evidence for reductive activation by human NADPH:cytochrome P450 reductase. Chem Res Toxicol. 2008 Dec;21(12):2393-406. doi: 10.1021/tx800281h. [PubMed:19548358 ]
  3. Gan L, von Moltke LL, Trepanier LA, Harmatz JS, Greenblatt DJ, Court MH: Role of NADPH-cytochrome P450 reductase and cytochrome-b5/NADH-b5 reductase in variability of CYP3A activity in human liver microsomes. Drug Metab Dispos. 2009 Jan;37(1):90-6. doi: 10.1124/dmd.108.023424. Epub 2008 Oct 6. [PubMed:18838505 ]
Enzyme Details
2. Lipoyl synthase, mitochondrial
General function:
Involved in catalytic activity
Specific function:
Catalyzes the radical-mediated insertion of two sulfur atoms into the C-6 and C-8 positions of the octanoyl moiety bound to the lipoyl domains of lipoate-dependent enzymes, thereby converting the octanoylated domains into lipoylated derivatives (By similarity).
Gene Name:
LIAS
Uniprot ID:
O43766
Molecular weight:
41910.695
References
  1. Morikawa T, Yasuno R, Wada H: Do mammalian cells synthesize lipoic acid? Identification of a mouse cDNA encoding a lipoic acid synthase located in mitochondria. FEBS Lett. 2001 Jun 1;498(1):16-21. [PubMed:11389890 ]
  2. Yasuno R, Wada H: Biosynthesis of lipoic acid in Arabidopsis: cloning and characterization of the cDNA for lipoic acid synthase. Plant Physiol. 1998 Nov;118(3):935-43. [PubMed:9808738 ]
  3. Ollagnier-de Choudens S, Fontecave M: The lipoate synthase from Escherichia coli is an iron-sulfur protein. FEBS Lett. 1999 Jun 18;453(1-2):25-8. [PubMed:10403368 ]
  4. Wrenger C, Muller S: The human malaria parasite Plasmodium falciparum has distinct organelle-specific lipoylation pathways. Mol Microbiol. 2004 Jul;53(1):103-13. [PubMed:15225307 ]
  5. Gunther S, McMillan PJ, Wallace LJ, Muller S: Plasmodium falciparum possesses organelle-specific alpha-keto acid dehydrogenase complexes and lipoylation pathways. Biochem Soc Trans. 2005 Nov;33(Pt 5):977-80. [PubMed:16246025 ]
Enzyme Details
3. Sodium-dependent multivitamin transporter
General function:
Involved in transporter activity
Specific function:
Transports pantothenate, biotin and lipoate in the presence of sodium.
Gene Name:
SLC5A6
Uniprot ID:
Q9Y289
Molecular weight:
68641.27
References
  1. Prasad PD, Wang H, Huang W, Fei YJ, Leibach FH, Devoe LD, Ganapathy V: Molecular and functional characterization of the intestinal Na+-dependent multivitamin transporter. Arch Biochem Biophys. 1999 Jun 1;366(1):95-106. [PubMed:10334869 ]
  2. Dey S, Subramanian VS, Chatterjee NS, Rubin SA, Said HM: Characterization of the 5' regulatory region of the human sodium-dependent multivitamin transporter, hSMVT. Biochim Biophys Acta. 2002 Mar 19;1574(2):187-92. [PubMed:11955628 ]
  3. Griffin JB, Stanley JS, Zempleni J: Synthesis of a rabbit polyclonal antibody to the human sodium-dependent multivitamin transporter. Int J Vitam Nutr Res. 2002 Jul;72(4):195-8. [PubMed:12214555 ]
Enzyme Details
4. Acyl-coenzyme A synthetase ACSM1, mitochondrial
General function:
Involved in catalytic activity
Specific function:
Has medium-chain fatty acid:CoA ligase activity with broad substrate specificity (in vitro). Acts on acids from C(4) to C(11) and on the corresponding 3-hydroxy- and 2,3- or 3,4-unsaturated acids (in vitro). Functions as GTP-dependent lipoate-activating enzyme that generates the substrate for lipoyltransferase (By similarity).
Gene Name:
ACSM1
Uniprot ID:
Q08AH1
Molecular weight:
65272.74
Reactions
Guanosine triphosphate + (S)-lipoic acid → Pyrophosphate + lipoyl-GMPdetails
Enzyme Details
5. Lipoyltransferase 1, mitochondrial
General function:
Involved in catalytic activity
Specific function:
Catalyzes the transfer of the lipoyl group from lipoyl-AMP to the specific lysine residue of lipoyl domains of lipoate-dependent enzymes (By similarity).
Gene Name:
LIPT1
Uniprot ID:
Q9Y234
Molecular weight:
42478.8
References
  1. Gunther S, McMillan PJ, Wallace LJ, Muller S: Plasmodium falciparum possesses organelle-specific alpha-keto acid dehydrogenase complexes and lipoylation pathways. Biochem Soc Trans. 2005 Nov;33(Pt 5):977-80. [PubMed:16246025 ]
  2. Fujiwara K, Toma S, Okamura-Ikeda K, Motokawa Y, Nakagawa A, Taniguchi H: Crystal structure of lipoate-protein ligase A from Escherichia coli. Determination of the lipoic acid-binding site. J Biol Chem. 2005 Sep 30;280(39):33645-51. Epub 2005 Jul 25. [PubMed:16043486 ]
  3. Gueguen V, Macherel D, Neuburger M, Pierre CS, Jaquinod M, Gans P, Douce R, Bourguignon J: Structural and functional characterization of H protein mutants of the glycine decarboxylase complex. J Biol Chem. 1999 Sep 10;274(37):26344-52. [PubMed:10473591 ]
  4. Macherel D, Bourguignon J, Forest E, Faure M, Cohen-Addad C, Douce R: Expression, lipoylation and structure determination of recombinant pea H-protein in Escherichia coli. Eur J Biochem. 1996 Feb 15;236(1):27-33. [PubMed:8617275 ]
  5. Fujiwara K, Hosaka H, Matsuda M, Okamura-Ikeda K, Motokawa Y, Suzuki M, Nakagawa A, Taniguchi H: Crystal structure of bovine lipoyltransferase in complex with lipoyl-AMP. J Mol Biol. 2007 Aug 3;371(1):222-34. Epub 2007 May 26. [PubMed:17570395 ]