Lipoic acid (ECMDB01451) (M2MDB000392)

IdentificationTaxonomyPhysical PropertiesBiological PropertiesSpectraConcentrationsLinksReferencesEnzymes (1)Transporters (4)XML
Proteins (5)
Record Information
Version2.0
Creation Date2012-05-31 13:52:59 -0600
Update Date2015-09-13 12:56:11 -0600
Secondary Accession Numbers
  • ECMDB01451
Identification
Name:Lipoic acid
DescriptionLipoic acid is a vitamin-like antioxidant that acts as a free-radical scavenger. Alpha-lipoic acid is also known as thioctic acid. Lipoic acid contains two thiol groups which may be either oxidized or reduced. The reduced form is known as dihydrolipoic acid (DHLA). Lipoic acid (Delta E= -0.288) is therefore capable of thiol-disulfide exchange, giving it antioxidant activity. Lipoate is a critical cofactor for aerobic metabolism, participating in the transfer of acyl or methylamine groups via the 2-Oxoacid dehydrogenase (2-OADH) or alpha-ketoglutarate dehydrogenase complex. This enzyme catalyzes the conversion of alpha-ketoglutarate to succinyl CoA. This activity results in the catabolism of the branched chain amino acids (leucine, isoleucine and valine). Lipoic acid also participates in the glycine cleavage system(GCV). The glycine cleavage system is a multi-enzyme complex that catalyzes the oxidation of glycine to form 5,10 methylene tetrahydrofolate, an important cofactor in nucleic acid synthesis. Since Lipoic acid is an essential cofactor for many enzyme complexes, it is essential for aerobic life as we know it. Lipoic acid was first postulated to be an effective antioxidant when it was found it prevented vitamin C and vitamin E deficiency. It is able to scavenge reactive oxygen species and reduce other metabolites, such as glutathione or vitamins, maintaining a healthy cellular redox state. Lipoic acid has been shown in cell culture experiments to increase cellular uptake of glucose by recruiting the glucose transporter GLUT4 to the cell membrane. (Wikipedia)
Structure
Thumb
MOLSDF3D-SDFPDBSMILESInChI View 3D Structure
Synonyms:
  • α-liponate
  • α-liponic acid
  • (+)-a-Lipoate
  • (+)-a-Lipoic acid
  • (+)-alpha-Lipoate
  • (+)-alpha-Lipoic acid
  • (+)-α-Lipoate
  • (+)-α-Lipoic acid
  • (+-)-1,2-Dithiolane-3-pentanoate
  • (+-)-1,2-Dithiolane-3-pentanoic acid
  • (+-)-1,2-Dithiolane-3-valerate
  • (+-)-1,2-Dithiolane-3-valeric acid
  • (R)-1,2-Dithiolane-3-pentanoate
  • (R)-1,2-Dithiolane-3-pentanoic acid
  • (RS)-a-Lipoate
  • (RS)-a-Lipoic acid
  • (RS)-alpha-Lipoate
  • (RS)-alpha-Lipoic acid
  • (RS)-Lipoate
  • (RS)-Lipoic acid
  • (RS)-α-Lipoate
  • (RS)-α-Lipoic acid
  • 1,2-Dithiolane-3-pentanoate
  • 1,2-Dithiolane-3-pentanoic acid
  • 1,2-Dithiolane-3-valerate
  • 1,2-Dithiolane-3-valeric acid
  • 1,2-Dithiolane-3R-pentanoate
  • 1,2-Dithiolane-3R-pentanoic acid
  • 5-(1,2-Dithiolan-3-yl)-pentanoate
  • 5-(1,2-Dithiolan-3-yl)-pentanoic acid
  • 5-(1,2-Dithiolan-3-yl)pentanoate
  • 5-(1,2-Dithiolan-3-yl)pentanoic acid
  • 5-(1,2-Dithiolan-3-yl)valerate
  • 5-(1,2-Dithiolan-3-yl)valeric acid
  • 5-(Dithiolan-3-yl)valerate
  • 5-(Dithiolan-3-yl)valeric acid
  • 5-[3-(1,2-Dithiolanyl)]pentanoate
  • 5-[3-(1,2-Dithiolanyl)]pentanoic acid
  • 6,8-Dithiooctanoate
  • 6,8-Dithiooctanoic acid
  • 6,8-Thioctate
  • 6,8-Thioctic acid
  • 6,8-Thiotate
  • 6,8-Thiotic acid
  • 6-Thioctate
  • 6-Thioctic acid
  • 6-Thiotate
  • 6-Thiotic acid
  • a Lipoate
  • a Lipoic acid
  • a-Lipoate
  • a-Lipoic acid
  • a-Liponate
  • a-Liponic acid
  • a-Liponsaeure
  • Acetate replacing factor
  • Acetate-replacing factor
  • Acetic acid replacing factor
  • Acetic acid-replacing factor
  • Alpha Lipoate
  • Alpha Lipoic acid
  • Alpha-Lipoate
  • Alpha-Lipoic acid
  • Alpha-Liponate
  • Alpha-Liponic acid
  • Alpha-Liponsaeure
  • Biletan
  • Delta-[3-(1,2-Dithiacyclopentyl)]pentanoate
  • Delta-[3-(1,2-Dithiacyclopentyl)]pentanoic acid
  • DL-1,2-Dithiolane 3-valerate
  • DL-1,2-Dithiolane 3-valeric acid
  • DL-6,8-Dithiooctanoate
  • DL-6,8-Dithiooctanoic acid
  • DL-6,8-Thioctate
  • DL-6,8-Thioctic acid
  • DL-6-Thioctate
  • DL-6-Thioctic acid
  • DL-a-Lipoate
  • DL-a-Lipoic acid
  • DL-alpha-Lipoate
  • DL-alpha-Lipoic acid
  • Dl-Lipoate
  • Dl-Lipoic acid
  • Dl-Thioctate
  • DL-Thioctate > 98%
  • Dl-Thioctic acid
  • DL-Thioctic acid > 98%
  • DL-α-Lipoate
  • DL-α-Lipoic acid
  • Heparlipon
  • Lip
  • Lipoate
  • Lipoic acid
  • Liponate
  • Liponic acid
  • Liposan
  • Lipothion
  • Protogen A
  • Pyruvate oxidation factor
  • Pyruvic acid oxidation factor
  • R-Lipoate
  • R-Lipoic acid
  • Rac-lipoate
  • Rac-lipoic acid
  • Thioctacid
  • Thioctan
  • Thioctate
  • Thioctate D-form
  • Thioctate dl-form
  • Thioctic acid
  • Thioctic acid D-form
  • Thioctic acid dl-form
  • Thioctidase
  • Thioctsan
  • Thioktsaeure
  • Thiooctanoate
  • Thiooctanoic acid
  • Tioctacid
  • Tioctan
  • Tioctidasi
  • Tioctidasi acetate replacing factor
  • Tioctidasi acetic acid replacing factor
  • α Lipoate
  • α Lipoic acid
  • α-Lipoate
  • α-Lipoic acid
  • α-Liponate
  • α-Liponic acid
  • α-Liponsaeure
  • δ-[3-(1,2-Dithiacyclopentyl)]pentanoate
  • δ-[3-(1,2-Dithiacyclopentyl)]pentanoic acid
Chemical Formula:C8H14O2S2
Weight:Average: 206.326
Monoisotopic: 206.043521072
InChI Key:AGBQKNBQESQNJD-SSDOTTSWSA-N
InChI: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
CAS number:1077-28-7
IUPAC Name:5-[(3R)-1,2-dithiolan-3-yl]pentanoic acid
Traditional IUPAC Name:lipoic acid
SMILES:OC(=O)CCCC[C@@H]1CCSS1
Chemical Taxonomy
Description belongs to the class of organic compounds known as lipoic acids and derivatives. Lipoic acids and derivatives 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
Physical Properties
State:Solid
Charge:-1
Melting point:60.5 °C
Experimental Properties:
PropertyValueSource
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
Biological Properties
Cellular Locations:Cytoplasm
Reactions:
Adenosine triphosphate + Lipoic acid > Lipoyl-AMP + Pyrophosphate
Adenosine triphosphate + Lipoic acid <> Pyrophosphate + Lipoyl-AMP
Hydrogen ion + Lipoic acid + Adenosine triphosphate > Lipoyl-AMP + Pyrophosphate
(R)-lipoic acid + Adenosine triphosphate + Hydrogen ion + Lipoic acid > Pyrophosphate + Lipoyl-AMP + Lipoyl-AMP
SMPDB Pathways:
Lipoic acid metabolismPW000770 ThumbThumb?image type=greyscaleThumb?image type=simple
KEGG Pathways:
EcoCyc Pathways:
Concentrations
Not Available
Spectra
Spectra:
Spectrum TypeDescriptionSplash Key
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-0aba-3900000000-46fc1d57abcc26f6720eView in MoNA
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-0aba-3900000000-46fc1d57abcc26f6720eView in MoNA
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-0aba-3900000000-46fc1d57abcc26f6720eView in MoNA
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
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot AvailableView in JSpectraViewer
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
LC-MS/MSLC-MS/MS Spectrum - 20V, Negativesplash10-03di-9100000000-e420d2c931e889befcfaView in MoNA
LC-MS/MSLC-MS/MS Spectrum - 10V, Negativesplash10-0229-6900000000-90386d8704ab5bfe8e70View in MoNA
LC-MS/MSLC-MS/MS Spectrum - 40V, Negativesplash10-03di-9000000000-042d27906c9bde31821fView in MoNA
LC-MS/MSLC-MS/MS Spectrum - 35V, Negativesplash10-03di-9000000000-6572cec5a1c9f68d9679View 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
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-0970000000-0ae5b11a032d11c1ba6dView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-03di-1900000000-decf255617c1bbd69bfbView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-000i-6900000000-eb58a3d8135ba85d4283View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0a4i-0190000000-014d2ea36cfae0726a9eView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0a4i-5950000000-4e2dd5ccdcd5b0a936a0View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0a59-9500000000-9bbbd7b252fb9a0b438dView in MoNA
1D NMR1H NMR SpectrumNot AvailableView in JSpectraViewer
2D NMR[1H,13C] 2D NMR SpectrumNot AvailableView in JSpectraViewer
References
References:
  • Arner ES, Nordberg J, Holmgren A: Efficient reduction of lipoamide and lipoic acid by mammalian thioredoxin reductase. Biochem Biophys Res Commun. 1996 Aug 5;225(1):268-74. Pubmed: 8769129
  • Baker H, Deangelis B, Baker ER, Hutner SH: A practical assay of lipoate in biologic fluids and liver in health and disease. Free Radic Biol Med. 1998 Sep;25(4-5):473-9. Pubmed: 9741583
  • Barbiroli B, Medori R, Tritschler HJ, Klopstock T, Seibel P, Reichmann H, Iotti S, Lodi R, Zaniol P: Lipoic (thioctic) acid increases brain energy availability and skeletal muscle performance as shown by in vivo 31P-MRS in a patient with mitochondrial cytopathy. J Neurol. 1995 Jul;242(7):472-7. Pubmed: 7595680
  • Bruggraber SF, Leung PS, Amano K, Quan C, Kurth MJ, Nantz MH, Benson GD, Van de Water J, Luketic V, Roche TE, Ansari AA, Coppel RL, Gershwin ME: Autoreactivity to lipoate and a conjugated form of lipoate in primary biliary cirrhosis. Gastroenterology. 2003 Dec;125(6):1705-13. Pubmed: 14724823
  • Burke DG, Chilibeck PD, Parise G, Tarnopolsky MA, Candow DG: Effect of alpha-lipoic acid combined with creatine monohydrate on human skeletal muscle creatine and phosphagen concentration. Int J Sport Nutr Exerc Metab. 2003 Sep;13(3):294-302. Pubmed: 14669930
  • Chevion S, Hofmann M, Ziegler R, Chevion M, Nawroth PP: The antioxidant properties of thioctic acid: characterization by cyclic voltammetry. Biochem Mol Biol Int. 1997 Feb;41(2):317-27. Pubmed: 9063572
  • Haj-Yehia AI, Assaf P, Nassar T, Katzhendler J: Determination of lipoic acid and dihydrolipoic acid in human plasma and urine by high-performance liquid chromatography with fluorimetric detection. J Chromatogr A. 2000 Feb 18;870(1-2):381-8. Pubmed: 10722093
  • Henriksen EJ, Saengsirisuwan V: Exercise training and antioxidants: relief from oxidative stress and insulin resistance. Exerc Sport Sci Rev. 2003 Apr;31(2):79-84. Pubmed: 12715971
  • Kanehisa, M., Goto, S., Sato, Y., Furumichi, M., Tanabe, M. (2012). "KEGG for integration and interpretation of large-scale molecular data sets." Nucleic Acids Res 40:D109-D114. Pubmed: 22080510
  • Keseler, I. M., Collado-Vides, J., Santos-Zavaleta, A., Peralta-Gil, M., Gama-Castro, S., Muniz-Rascado, L., Bonavides-Martinez, C., Paley, S., Krummenacker, M., Altman, T., Kaipa, P., Spaulding, A., Pacheco, J., Latendresse, M., Fulcher, C., Sarker, M., Shearer, A. G., Mackie, A., Paulsen, I., Gunsalus, R. P., Karp, P. D. (2011). "EcoCyc: a comprehensive database of Escherichia coli biology." Nucleic Acids Res 39:D583-D590. Pubmed: 21097882
  • Konrad D: Utilization of the insulin-signaling network in the metabolic actions of alpha-lipoic acid-reduction or oxidation? Antioxid Redox Signal. 2005 Jul-Aug;7(7-8):1032-9. Pubmed: 15998258
  • Lee WJ, Lee IK, Kim HS, Kim YM, Koh EH, Won JC, Han SM, Kim MS, Jo I, Oh GT, Park IS, Youn JH, Park SW, Lee KU, Park JY: Alpha-lipoic acid prevents endothelial dysfunction in obese rats via activation of AMP-activated protein kinase. Arterioscler Thromb Vasc Biol. 2005 Dec;25(12):2488-94. Epub 2005 Oct 13. Pubmed: 16224049
  • Loginov AS, Nilova TV, Bendikov EA, Petrakov AV: [Pharmacokinetics of preparations of lipoic acid and their effect on ATP synthesis, processes of microsomal and cytosol oxidation in hepatocytes in liver damage in man] Farmakol Toksikol. 1989 Jul-Aug;52(4):78-82. Pubmed: 2509239
  • McCormick DB: A trail of research on cofactors: an odyssey with friends. J Nutr. 2000 Feb;130(2S Suppl):323S-330S. Pubmed: 10721897
  • Nagamatsu M, Nickander KK, Schmelzer JD, Raya A, Wittrock DA, Tritschler H, Low PA: Lipoic acid improves nerve blood flow, reduces oxidative stress, and improves distal nerve conduction in experimental diabetic neuropathy. Diabetes Care. 1995 Aug;18(8):1160-7. Pubmed: 7587852
  • Redden PR, Melanson RL, Douglas JA, Dick AJ: Acyloxymethyl acidic drug derivatives: in vitro hydrolytic reactivity. Int J Pharm. 1999 Apr 15;180(2):151-60. Pubmed: 10370185
  • Semenova TV, Azhitskii GIu, Sarnatskaia VV, Nikolaev VG: [Effect of various specific agents on the heat stability of human serum albumin] Ukr Biokhim Zh. 1993 Sep-Oct;65(5):26-30. Pubmed: 8160293
  • Steinmann B, Gitzelmann R: Strychnine treatment attempted in newborn twins with severe nonketotic hyperglycinemia. Helv Paediatr Acta. 1979;34(6):589-99. Pubmed: 541222
  • Tankova T, Cherninkova S, Koev D: Treatment for diabetic mononeuropathy with alpha-lipoic acid. Int J Clin Pract. 2005 Jun;59(6):645-50. Pubmed: 15924591
  • Teichert J, Tuemmers T, Achenbach H, Preiss C, Hermann R, Ruus P, Preiss R: Pharmacokinetics of alpha-lipoic acid in subjects with severe kidney damage and end-stage renal disease. J Clin Pharmacol. 2005 Mar;45(3):313-28. Pubmed: 15703366
  • van der Werf, M. J., Overkamp, K. M., Muilwijk, B., Coulier, L., Hankemeier, T. (2007). "Microbial metabolomics: toward a platform with full metabolome coverage." Anal Biochem 370:17-25. Pubmed: 17765195
  • Winder, C. L., Dunn, W. B., Schuler, S., Broadhurst, D., Jarvis, R., Stephens, G. M., Goodacre, R. (2008). "Global metabolic profiling of Escherichia coli cultures: an evaluation of methods for quenching and extraction of intracellular metabolites." Anal Chem 80:2939-2948. Pubmed: 18331064
Synthesis Reference:Not Available
Material Safety Data Sheet (MSDS)Download (PDF)
External Links:
ResourceLink
CHEBI ID16494
HMDB IDHMDB01451
Pubchem Compound ID864
Kegg IDC16241
ChemSpider ID5886
WikipediaLipoic acid
BioCyc IDLIPOIC-ACID
EcoCyc IDLIPOIC-ACID
Ligand ExpoLPA

Enzymes

Protein Details
1. Lipoate-protein ligase A
General function:
Involved in catalytic activity
Specific function:
Catalyzes both the ATP-dependent activation of exogenously supplied lipoate to lipoyl-AMP and the transfer of the activated lipoyl onto the lipoyl domains of lipoate-dependent enzymes. Is also able to catalyze very poorly the transfer of lipoyl and octanoyl moiety from their acyl carrier protein
Gene Name:
lplA
Uniprot ID:
P32099
Molecular weight:
37926
Reactions
ATP + lipoate = diphosphate + lipoyl-AMP.
Lipoyl-AMP + protein = protein N(6)-(lipoyl)lysine + AMP.

Transporters

Protein Details
1. Outer membrane protein N
General function:
Involved in transporter activity
Specific function:
Non-specific porin
Gene Name:
ompN
Uniprot ID:
P77747
Molecular weight:
41220
Protein Details
2. Outer membrane pore protein E
General function:
Involved in transporter activity
Specific function:
Uptake of inorganic phosphate, phosphorylated compounds, and some other negatively charged solutes
Gene Name:
phoE
Uniprot ID:
P02932
Molecular weight:
38922
Protein Details
3. Outer membrane protein F
General function:
Involved in transporter activity
Specific function:
OmpF is a porin that forms passive diffusion pores which allow small molecular weight hydrophilic materials across the outer membrane. It is also a receptor for the bacteriophage T2
Gene Name:
ompF
Uniprot ID:
P02931
Molecular weight:
39333
Protein Details
4. Outer membrane protein C
General function:
Involved in transporter activity
Specific function:
Forms passive diffusion pores which allow small molecular weight hydrophilic materials across the outer membrane
Gene Name:
ompC
Uniprot ID:
P06996
Molecular weight:
40368