You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on DrugBank.
Identification
NameLipoic Acid
Accession NumberDB00166  (NUTR00035)
TypeSmall Molecule
GroupsApproved, Nutraceutical
Description

A vitamin-like antioxidant. [PubChem]

Structure
Thumb
Synonyms
SynonymLanguageCode
1,2-dithiolane-3-pentanoic acidNot AvailableNot Available
1,2-dithiolane-3-valeric acidNot AvailableNot Available
5-(1,2-dithiolan-3-yl)valeric acidNot AvailableNot Available
5-(dithiolan-3-yl)valeric acidNot AvailableNot Available
5-[3-(1,2-dithiolanyl)]pentanoic acidNot AvailableNot Available
6-thioctic acidNot AvailableNot Available
6-thiotic acidNot AvailableNot Available
6,8-thioctic acidNot AvailableNot Available
6,8-thiotic acidNot AvailableNot Available
Acetate-replacing factorNot AvailableNot Available
alpha-Lipoic acidNot AvailableNot Available
alpha-LiponsaeureNot AvailableNot Available
BiletanNot AvailableNot Available
Lipoic acidNot AvailableNot Available
liponic acidNot AvailableNot Available
ThioctansaeureNot AvailableNot Available
Thioctic acidNot AvailableNot Available
ThioctsaeureNot AvailableNot Available
ThioktsaeureNot AvailableNot Available
α-lipoic acidNot AvailableNot Available
SaltsNot Available
Brand names
NameCompany
BiletanNot Available
Brand mixturesNot Available
Categories
CAS number62-46-4
WeightAverage: 206.326
Monoisotopic: 206.043521072
Chemical FormulaC8H14O2S2
InChI KeyAGBQKNBQESQNJD-UHFFFAOYSA-N
InChI
InChI=1S/C8H14O2S2/c9-8(10)4-2-1-3-7-5-6-11-12-7/h7H,1-6H2,(H,9,10)
IUPAC Name
5-(1,2-dithiolan-3-yl)pentanoic acid
SMILES
OC(=O)CCCCC1CCSS1
Mass Specshow(11.4 KB)
Taxonomy
KingdomOrganic Compounds
SuperclassHeterocyclic Compounds
ClassDithiolanes
SubclassLipoic Acid Derivatives
Direct parentLipoic Acid Derivatives
Alternative parentsHeterocyclic Fatty Acids; Organic Disulfides; Polyamines; Enolates; Carboxylic Acids
Substituentsorganic disulfide; polyamine; enolate; carboxylic acid; carboxylic acid derivative
Classification descriptionThis compound belongs to the lipoic acid derivatives. These are compounds containing a lipoic acid moiety (or a derivative thereof), which consistis of a pentanoic acid (or derivative) attached to the C3 carbon atom of a 1,2-dithiolane ring.
Pharmacology
IndicationFor nutritional supplementation, also for treating dietary shortage or imbalance.
PharmacodynamicsLipoic acid (or α-lipoic acid) is able to pass the blood-brain barrier and is putatively used for detoxification of mercury attached to the brain cells. It can mobilise bound mercury into the blood stream as it is a mercaptan (sulfur compound which readily binds to the mercury). In the blood stream, another chelator such as dimercaptosuccinic acid (DMSA) or methylsulfonylmethane (MSM) is used to transfer mercury safely into the urine for excretion. Neither DMSA nor MSM can cross the blood-brain barrier, which is why both lipoic acid and DMSA are used. It is hypothesized that this treatment-along with carnitine, dimethylglycine (DMG), Vitamin B6, folic acid, and magnesium—could be used to treat autism and amalgam poisoning. In this hypothesis, the reason why autism is difficult to treat is that mercury is attached to the brain cells and most medicines and vitamin supplements do not penetrate the blood-brain barrier. However, α-lipoic acid and perhaps vitamin B12 could making it possible for other chelators to remove mercury safely out of the body and could perhaps one day be used as a treatment for autism. Because lipoic acid is related to cellular uptake of glucose and it is both soluble in water and fat, it is being used for treatment in diabetes. It may be helpful for people with Alzheimer's disease or Parkinson's disease.
Mechanism of actionLipoic Acid is generally involved in oxidative decarboxylations of keto acids and is presented as a growth factor for some organisms. Lipoic acid exists as two enantiomers, the R-enantiomer and the S-enantiomer. Normally only the R-enantiomer of an amino acid is biologically active, but for lipoic acid the S-enantiomer assists in the reduction of the R-enantiomer when a racemic mixture is given. 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.
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
Metabolism
Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.9695
Blood Brain Barrier + 0.9749
Caco-2 permeable - 0.5385
P-glycoprotein substrate Non-substrate 0.7248
P-glycoprotein inhibitor I Non-inhibitor 0.9526
P-glycoprotein inhibitor II Non-inhibitor 0.9856
Renal organic cation transporter Non-inhibitor 0.8373
CYP450 2C9 substrate Non-substrate 0.7961
CYP450 2D6 substrate Non-substrate 0.8334
CYP450 3A4 substrate Non-substrate 0.7346
CYP450 1A2 substrate Non-inhibitor 0.9046
CYP450 2C9 substrate Non-inhibitor 0.9071
CYP450 2D6 substrate Non-inhibitor 0.9232
CYP450 2C19 substrate Non-inhibitor 0.9025
CYP450 3A4 substrate Non-inhibitor 0.9365
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9301
Ames test Non AMES toxic 0.9133
Carcinogenicity Non-carcinogens 0.8721
Biodegradation Ready biodegradable 0.7788
Rat acute toxicity 2.2921 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9452
hERG inhibition (predictor II) Non-inhibitor 0.9451
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage formsNot Available
Prices
Unit descriptionCostUnit
Lipoic acid powder77.35USDg
Lipoic acid capsule0.26USDcapsule
Alpha lipoic acid 200 mg tablet0.22USDtablet
Alpha-lipoic acid 50 mg caplet0.16USDcaplet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point60.5 °CPhysProp
boiling point162.5 °CPhysProp
water solubilityInsolubleNot Available
logP2.1Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.224ALOGPS
logP2.75ALOGPS
logP2.11ChemAxon
logS-3ALOGPS
pKa (Strongest Acidic)4.52ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area37.3 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity54.37 m3·mol-1ChemAxon
Polarizability22 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis Reference

Joachim Paust, Peter Eckes, Wolfgang Siegel, Friedhelm Balkenhohl, Walter Dobler, Michael Hullmann, “Preparation of R/S-.gamma.-lipoic acid or R/S-.alpha.-lipoic acid.” U.S. Patent US5489694, issued July, 1961.

US5489694
General Reference
  1. Perham RN: Swinging arms and swinging domains in multifunctional enzymes: catalytic machines for multistep reactions. Annu Rev Biochem. 2000;69:961-1004. Pubmed
  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
External Links
ResourceLink
KEGG DrugD00086
KEGG CompoundC00725
ChEBI16494
ChEMBLCHEMBL134342
PharmGKBPA164776929
HETLPA
WikipediaLipoic_Acid
ATC CodesA16AX01
AHFS CodesNot Available
PDB Entries
FDA labelNot Available
MSDSshow(73.1 KB)
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

1. Lipoyltransferase 1, mitochondrial

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Lipoyltransferase 1, mitochondrial Q9Y234 Details

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
  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
  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
  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
  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

2. Lipoyl synthase, mitochondrial

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Lipoyl synthase, mitochondrial O43766 Details

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
  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
  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
  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
  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

3. Sodium-dependent multivitamin transporter

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Sodium-dependent multivitamin transporter Q9Y289 Details

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
  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
  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

Enzymes

1. NADPH--cytochrome P450 reductase

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
NADPH--cytochrome P450 reductase P16435 Details

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
  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. Pubmed
  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. Epub 2008 Oct 6. Pubmed

Comments
comments powered by Disqus
Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:08