Human Metabolome Database Version 3.5

Showing metabocard for (R)-lipoic acid (HMDB01451)

Record Information
Version 3.5
Creation Date 2005-11-16 08:48:42 -0700
Update Date 2013-06-30 11:10:13 -0600
HMDB ID HMDB01451
Secondary Accession Numbers None
Metabolite Identification
Common Name (R)-lipoic acid
Description Lipoic 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
Download: MOL | SDF | PDB | SMILES | InChI
Display: 2D Structure | 3D Structure
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 Formula C8H14O2S2
Average Molecular Weight 206.326
Monoisotopic Molecular Weight 206.043521072
IUPAC Name 5-[(3R)-1,2-dithiolan-3-yl]pentanoic acid
Traditional IUPAC Name lipoic acid
CAS Registry Number 1200-22-2
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 Key AGBQKNBQESQNJD-JLDDOWRYNA-N
Chemical Taxonomy
Kingdom Organic Compounds
Super Class Aliphatic Heteromonocyclic Compounds
Class Dithiolanes
Sub Class Lipoic 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 Parent Lipoic Acid Derivatives
Ontology
Status Detected and Quantified
Origin
  • Endogenous
Biofunction
  • Enzyme co-factor
Application Not Available
Cellular locations
  • Cytoplasm
  • Extracellular
  • Membrane (predicted from logP)
Physical Properties
State Solid
Experimental Properties
Property Value Reference
Melting Point 60.5 °C Not Available
Boiling Point Not Available Not Available
Water Solubility Not Available Not Available
LogP Not Available Not Available
Predicted Properties
Property Value Source
Water Solubility 0.22 g/L ALOGPS
LogP 2.75 ALOGPS
LogP 2.11 ChemAxon
LogS -2.96 ALOGPS
pKa (strongest acidic) 4.52 ChemAxon
Hydrogen Acceptor Count 2 ChemAxon
Hydrogen Donor Count 1 ChemAxon
Polar Surface Area 37.3 A2 ChemAxon
Rotatable Bond Count 5 ChemAxon
Refractivity 54.37 ChemAxon
Polarizability 21.74 ChemAxon
Formal Charge 0 ChemAxon
Physiological Charge -1 ChemAxon
Spectra
Not Available
Biological Properties
Cellular Locations
  • Cytoplasm
  • Extracellular
  • Membrane (predicted from logP)
Biofluid Locations
  • Blood
Tissue Location
  • Muscle
  • Skeletal Muscle
  • Placenta
  • Kidney
  • Liver
  • Nerve Cells
Pathways
Name SMPDB Link KEGG Link
Ammonia Recycling SMP00009 map00910 Link_out
Glycine and Serine Metabolism SMP00004 map00260 Link_out
Normal Concentrations
Biofluid Status Value Age Sex Condition Reference
Blood Detected and Quantified
0.077 +/- 0.017 uM Adult (>18 years old) Both Normal
  • Geigy Scient...
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease References None
Associated OMIM IDs None
DrugBank ID Not Available
DrugBank Metabolite ID Not Available
Phenol Explorer Compound ID Not Available
Phenol Explorer Metabolite ID Not Available
FoodDB ID FDB022631
KNApSAcK ID Not Available
Chemspider ID 5886 Link_out
KEGG Compound ID C00725 Link_out
BioCyc ID LIPOIC-ACID Link_out
BiGG ID 35801 Link_out
Wikipedia Link Lipoic acid Link_out
NuGOwiki Link HMDB01451 Link_out
Metagene Link HMDB01451 Link_out
METLIN ID 126 Link_out
PubChem Compound 6112 Link_out
PDB ID LPA Link_out
ChEBI ID 30314 Link_out
References
Synthesis Reference Not Available
Material Safety Data Sheet (MSDS) Download (PDF)
General References
  1. 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 Link_out
  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 Link_out
  3. 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 Link_out
  4. 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 Link_out
  5. 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 Link_out
  6. 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 Link_out
  7. 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 Link_out
  8. 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 Link_out
  9. 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 Link_out
  10. 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 Link_out
  11. 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 Link_out
  12. 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 Link_out
  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 Link_out
  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 Link_out
  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 Link_out
  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 Link_out
  17. McCormick DB: A trail of research on cofactors: an odyssey with friends. J Nutr. 2000 Feb;130(2S Suppl):323S-330S. Pubmed: 10721897 Link_out
  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 Link_out

Enzymes
Name: Pyruvate dehydrogenase protein X component, mitochondrial
Reactions: Not Available
Gene Name: PDHX
Uniprot ID: O00330 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
Name: Dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex, mitochondrial
Reactions: Not Available
Gene Name: DLAT
Uniprot ID: P10515 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
Name: NADPH--cytochrome P450 reductase
Reactions: Not Available
Gene Name: POR
Uniprot ID: P16435 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
Name: Dihydrolipoyllysine-residue succinyltransferase component of 2-oxoglutarate dehydrogenase complex, mitochondrial
Reactions: Not Available
Gene Name: DLST
Uniprot ID: P36957 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
Name: Glycine cleavage system H protein, mitochondrial
Reactions: Not Available
Gene Name: GCSH
Uniprot ID: P23434 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
Name: Lipoamide acyltransferase component of branched-chain alpha-keto acid dehydrogenase complex, mitochondrial
Reactions: Not Available
Gene Name: DBT
Uniprot ID: P11182 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
Name: 3-oxoacyl-[acyl-carrier-protein] synthase, mitochondrial
Reactions: Not Available
Gene Name: OXSM
Uniprot ID: Q9NWU1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
Name: Lipoyltransferase 1, mitochondrial
Reactions: Not Available
Gene Name: LIPT1
Uniprot ID: Q9Y234 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA