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Record Information
Version3.6
Creation Date2005-11-16 15:48:42 UTC
Update Date2013-06-30 17:10:13 UTC
HMDB IDHMDB01451
Secondary Accession NumbersNone
Metabolite Identification
Common Name(R)-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. It is a naturally occurring compound that is synthesized by both plants and animals. 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. This system is used by many organisms and plays a crucial role in the photosynthetic carbon cycle. 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, suggesting its use in diabetes. Studies of rat aging have suggested that the use of L-carnitine and lipoic acid results in improved memory performance and delayed structural mitochondrial decay. As a result, it may be helpful for people with Alzheimer's disease or Parkinson's disease. -- Wikipedia.
Structure
Thumb
Synonyms
  1. (+)-alpha-Lipoic acid
  2. (R)-(+)-lipoic acid
  3. (R)-1,2-Dithiolane-3-pentanoic acid
  4. (R)-1,2-dithiolane-3-valeric acid
  5. (R)-6,8-thioctic acid
  6. alpha-Lipoic acid
  7. Lipoic acid
  8. R-LA
  9. RLA
  10. Thioctic acid
  11. Thioctic acid d-form
Chemical FormulaC8H14O2S2
Average Molecular Weight206.326
Monoisotopic Molecular Weight206.043521072
IUPAC Name5-[(3R)-1,2-dithiolan-3-yl]pentanoic acid
Traditional IUPAC Namelipoic acid
CAS Registry Number1200-22-2
SMILES
OC(=O)CCCC[C@@H]1CCSS1
InChI Identifier
InChI=1/C8H14O2S2/c9-8(10)4-2-1-3-7-5-6-11-12-7/h7H,1-6H2,(H,9,10)/t7-/s2
InChI KeyAGBQKNBQESQNJD-JLDDOWRYNA-N
Chemical Taxonomy
KingdomOrganic Compounds
Super ClassAliphatic Heteromonocyclic Compounds
ClassDithiolanes
Sub ClassLipoic Acid Derivatives
Other Descriptors
  • Heterocyclic Fatty Acids
  • Organic Compounds
  • Thia Fatty Acids
  • Thia fatty acids(KEGG)
  • Thia fatty acids(Lipidmaps)
  • dithiolanes(ChEBI)
  • heterocyclic fatty acid(ChEBI)
  • lipoic acid(ChEBI)
  • thia fatty acid(ChEBI)
Substituents
  • Carboxylic Acid
  • Organic Disulfide
Direct ParentLipoic Acid Derivatives
Ontology
StatusDetected and Quantified
Origin
  • Endogenous
Biofunction
  • Enzyme co-factor
ApplicationNot Available
Cellular locations
  • Cytoplasm
  • Extracellular
  • Membrane (predicted from logP)
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point60.5 °CNot Available
Boiling PointNot AvailableNot Available
Water SolubilityNot AvailableNot Available
LogPNot AvailableNot 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 area37.3ChemAxon
rotatable bond count5ChemAxon
refractivity54.37ChemAxon
polarizability21.74ChemAxon
Spectra
SpectraNot Available
Biological Properties
Cellular Locations
  • Cytoplasm
  • Extracellular
  • Membrane (predicted from logP)
Biofluid Locations
  • Blood
Tissue Location
  • Kidney
  • Liver
  • Muscle
  • Nerve Cells
  • Placenta
  • Skeletal Muscle
Pathways
NameSMPDB LinkKEGG Link
Ammonia RecyclingSMP00009map00910
Glycine and Serine MetabolismSMP00004map00260
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified0.077 +/- 0.017 uMAdult (>18 years old)BothNormal
    • Geigy Scientific ...
details
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDNot Available
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDFDB022631
KNApSAcK IDNot Available
Chemspider ID5886
KEGG Compound IDC00725
BioCyc IDLIPOIC-ACID
BiGG ID35801
Wikipedia LinkLipoic acid
NuGOwiki LinkHMDB01451
Metagene LinkHMDB01451
METLIN ID126
PubChem Compound6112
PDB IDLPA
ChEBI ID30314
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Download (PDF)
General References
  1. 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
  2. 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
  3. 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
  4. 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
  5. 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
  6. 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
  7. 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
  8. 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
  9. 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
  10. 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
  11. 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
  12. 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
  13. 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
  14. 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
  15. Steinmann B, Gitzelmann R: Strychnine treatment attempted in newborn twins with severe nonketotic hyperglycinemia. Helv Paediatr Acta. 1979;34(6):589-99. Pubmed: 541222
  16. 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
  17. McCormick DB: A trail of research on cofactors: an odyssey with friends. J Nutr. 2000 Feb;130(2S Suppl):323S-330S. Pubmed: 10721897
  18. 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

Enzymes

General function:
Involved in acyltransferase activity
Specific function:
Required for anchoring dihydrolipoamide dehydrogenase (E3) to the dihydrolipoamide transacetylase (E2) core of the pyruvate dehydrogenase complexes of eukaryotes. This specific binding is essential for a functional PDH complex
Gene Name:
PDHX
Uniprot ID:
O00330
Molecular weight:
54121.8
General function:
Involved in acyltransferase activity
Specific function:
The pyruvate dehydrogenase complex catalyzes the overall conversion of pyruvate to acetyl-CoA and CO(2), and thereby links the glycolytic pathway to the tricarboxylic cycle.
Gene Name:
DLAT
Uniprot ID:
P10515
Molecular weight:
68996.03
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
General function:
Involved in acyltransferase activity
Specific function:
The 2-oxoglutarate dehydrogenase complex catalyzes the overall conversion of 2-oxoglutarate to succinyl-CoA and CO(2). It contains multiple copies of 3 enzymatic components: 2-oxoglutarate dehydrogenase (E1), dihydrolipoamide succinyltransferase (E2) and lipoamide dehydrogenase (E3).
Gene Name:
DLST
Uniprot ID:
P36957
Molecular weight:
48754.87
General function:
Involved in glycine catabolic process
Specific function:
The glycine cleavage system catalyzes the degradation of glycine. The H protein shuttles the methylamine group of glycine from the P protein to the T protein.
Gene Name:
GCSH
Uniprot ID:
P23434
Molecular weight:
Not Available
General function:
Involved in acyltransferase activity
Specific function:
The branched-chain alpha-keto dehydrogenase complex catalyzes the overall conversion of alpha-keto acids to acyl-CoA and CO(2). It contains multiple copies of three enzymatic components: branched-chain alpha-keto acid decarboxylase (E1), lipoamide acyltransferase (E2) and lipoamide dehydrogenase (E3).
Gene Name:
DBT
Uniprot ID:
P11182
Molecular weight:
53486.635
General function:
Involved in catalytic activity
Specific function:
May play a role in the biosynthesis of lipoic acid as well as longer chain fatty acids required for optimal mitochondrial function.
Gene Name:
OXSM
Uniprot ID:
Q9NWU1
Molecular weight:
40034.535
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