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targets (3) enzymes (1)
for drugs
Identification
Name Lipoic Acid
Accession Number DB00166 (NUTR00035)
Type small molecule
Groups approved, nutraceutical
Description

A vitamin-like antioxidant. [PubChem]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
1,2-Dithiolane-3R-pentanoic acid
alpha-Lipoic acid
Lipoate
Thioctic acid
Salts Not Available
Brand names
Name Company
Biletan
Heparlipon
Thioctsan
Brand mixtures Not Available
Categories
  • Dietary supplement
  • Micronutrient
  • Vitamins (Vitamin B Complex)
  • Antioxidants
  • Vitamin B Complex
CAS number 62-46-4
Weight Average: 206.326
Monoisotopic: 206.043521072
Chemical Formula C8H14O2S2
InChI Key InChIKey=AGBQKNBQESQNJD-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)
Plain Text
IUPAC Name
5-(1,2-dithiolan-3-yl)pentanoic acid
SMILES
OC(=O)CCCCC1CCSS1
Plain Text
Mass Spec show (11.4 KB)
Taxonomy
Kingdom Not Available
Classes Not Available
Substructures Not Available
Pharmacology
Indication For nutritional supplementation, also for treating dietary shortage or imbalance.
Pharmacodynamics Lipoic 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 action Lipoic 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.
Absorption Not Available
Volume of distribution Not Available
Protein binding Not Available
Metabolism Not Available
Route of elimination Not Available
Half life Not Available
Clearance Not Available
Toxicity Not Available
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers Not Available
Packagers
Dosage forms Not Available
Prices
Unit description Cost Unit
Lipoic acid powder 77.35 USD g
Lipoic acid capsule 0.26 USD capsule
Alpha lipoic acid 200 mg tablet 0.22 USD tablet
Alpha-lipoic acid 50 mg caplet 0.16 USD caplet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents Not Available
Properties
State solid
Experimental Properties
Property Value Source
melting point 60.5 °C PhysProp
boiling point 162.5 °C PhysProp
water solubility Insoluble Not Available
logP 2.1 Not Available
Predicted Properties
Property Value Source
water solubility 2.24e-01 g/l ALOGPS
logP 2.75 ALOGPS
logP 2.11 ChemAxon
logS -3 ALOGPS
pKa (strongest acidic) 4.52 ChemAxon
physiological charge -1 ChemAxon
hydrogen acceptor count 2 ChemAxon
hydrogen donor count 1 ChemAxon
polar surface area 37.3 ChemAxon
rotatable bond count 5 ChemAxon
refractivity 54.37 ChemAxon
polarizability 22 ChemAxon
References
Synthesis Reference Not Available
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
Resource Link
KEGG Drug D00086 Link_out
KEGG Compound C00725 Link_out
ChEBI 16494 Link_out
ChEMBL 16494 Link_out
PharmGKB PA164776929 Link_out
HET LPA Link_out
Wikipedia http://en.wikipedia.org/wiki/Lipoic_Acid Link_out
ATC Codes
  • A16AX01
AHFS Codes Not Available
PDB Entries
FDA label Not Available
MSDS show (73.1 KB)
Interactions
Drug Interactions Not Available
Food Interactions Not Available
Targets

1. Lipoyltransferase 1, mitochondrial

Pharmacological action: unknown

Catalyzes the transfer of the lipoyl group from lipoyl- AMP to the specific lysine residue of the lipoate-dependent enzymes

Organism class: human
UniProt ID: Q9Y234 Link_out
Gene: LIPT1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Lipoic acid synthetase, mitochondrial

Pharmacological action: unknown

Synthesis of alpha-(+)-lipoic acid. It may be involved in the sulfur insertion chemistry in lipoate biosynthesis

Organism class: human
UniProt ID: O43766 Link_out
Gene: LIAS Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: unknown

Transports pantothenate, biotin and lipoate in the presence of sodium

Organism class: human
UniProt ID: Q9Y289 Link_out
Gene: SLC5A6 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Actions: inhibitor

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

UniProt ID: P16435 Link_out
Gene: POR Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19