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Identification
NameLipoic Acid
Accession NumberDB00166  (NUTR00035)
TypeSmall Molecule
GroupsApproved, Nutraceutical
Description

A vitamin-like antioxidant. [PubChem]

Structure
Thumb
Synonyms
1,2-dithiolane-3-pentanoic acid
1,2-dithiolane-3-valeric acid
5-(1,2-dithiolan-3-yl)valeric acid
5-(dithiolan-3-yl)valeric acid
5-[3-(1,2-dithiolanyl)]pentanoic acid
6-thioctic acid
6-thiotic acid
6,8-thioctic acid
6,8-thiotic acid
Acetate-replacing factor
alpha-Lipoic acid
alpha-Liponsäure
Biletan
liponic acid
Thioctansäure
Thioctic acid
Thioctsäure
Thioktsäure
α-lipoic acid
External Identifiers Not Available
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
BiletanNot Available
Brand mixtures
NameLabellerIngredients
Strovite One CapletsEverett Laboratories, Inc.
SaltsNot Available
Categories
UNII73Y7P0K73Y
CAS number62-46-4
WeightAverage: 206.326
Monoisotopic: 206.043521072
Chemical FormulaC8H14O2S2
InChI KeyInChIKey=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)
IUPAC Name
5-(1,2-dithiolan-3-yl)pentanoic acid
SMILES
OC(=O)CCCCC1CCSS1
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as lipoic acids and derivatives. These 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
  • Thia fatty acid
  • Heterocyclic fatty acid
  • Fatty acyl
  • Fatty acid
  • 1,2-dithiolane
  • Organic disulfide
  • Monocarboxylic acid or derivatives
  • Carboxylic acid
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organooxygen compound
  • Carbonyl group
  • Aliphatic heteromonocyclic compound
Molecular FrameworkAliphatic heteromonocyclic compounds
External Descriptors
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.
Related Articles
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
MetabolismNot Available
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
PropertyValueProbability
Human Intestinal Absorption+0.9695
Blood Brain Barrier+0.9749
Caco-2 permeable-0.5385
P-glycoprotein substrateNon-substrate0.7248
P-glycoprotein inhibitor INon-inhibitor0.9526
P-glycoprotein inhibitor IINon-inhibitor0.9856
Renal organic cation transporterNon-inhibitor0.8373
CYP450 2C9 substrateNon-substrate0.7961
CYP450 2D6 substrateNon-substrate0.8334
CYP450 3A4 substrateNon-substrate0.7346
CYP450 1A2 substrateNon-inhibitor0.9046
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorNon-inhibitor0.9232
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.9365
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9301
Ames testNon AMES toxic0.9133
CarcinogenicityNon-carcinogens0.8721
BiodegradationReady biodegradable0.7788
Rat acute toxicity2.2921 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9452
hERG inhibition (predictor II)Non-inhibitor0.9451
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage forms
FormRouteStrength
Tabletoral
Prices
Unit descriptionCostUnit
Lipoic acid powder77.35USD g
Lipoic acid capsule0.26USD capsule
Alpha lipoic acid 200 mg tablet0.22USD tablet
Alpha-lipoic acid 50 mg caplet0.16USD caplet
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 Solubility0.224 mg/mLALOGPS
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 RuleYesChemAxon
Spectra
Mass Spec (NIST)Download (11.4 KB)
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-052r-0920000000-cf913d1d1afc04e5450cView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0bti-5910000000-294c510229247ef63f20View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0bvi-9600000000-f8f54eb79c5d4d5bef48View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0a4i-0920000000-5a823a30dd1fb434e5b1View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0kmu-1910000000-6f491a68afd82922e71bView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0a4i-9200000000-330e4766f82ed571497bView in MoNA
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 References
  1. Perham RN: Swinging arms and swinging domains in multifunctional enzymes: catalytic machines for multistep reactions. Annu Rev Biochem. 2000;69:961-1004. [PubMed:10966480 ]
  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:14854913 ]
External Links
ATC CodesA16AX01
AHFS CodesNot Available
PDB Entries
FDA labelNot Available
MSDSDownload (73.1 KB)
Interactions
Drug Interactions
Drug
AcarboseLipoic Acid may increase the hypoglycemic activities of Acarbose.
AlbiglutideLipoic Acid may increase the hypoglycemic activities of Albiglutide.
AlogliptinLipoic Acid may increase the hypoglycemic activities of Alogliptin.
BromocriptineLipoic Acid may increase the hypoglycemic activities of Bromocriptine.
Calcium AcetateCalcium Acetate can cause a decrease in the absorption of Lipoic Acid resulting in a reduced serum concentration and potentially a decrease in efficacy.
Calcium carbonateCalcium carbonate can cause a decrease in the absorption of Lipoic Acid resulting in a reduced serum concentration and potentially a decrease in efficacy.
Calcium citrateCalcium citrate can cause a decrease in the absorption of Lipoic Acid resulting in a reduced serum concentration and potentially a decrease in efficacy.
Calcium gluconateCalcium gluconate can cause a decrease in the absorption of Lipoic Acid resulting in a reduced serum concentration and potentially a decrease in efficacy.
ChlorpropamideLipoic Acid may increase the hypoglycemic activities of Chlorpropamide.
CisplatinThe therapeutic efficacy of Cisplatin can be decreased when used in combination with Lipoic Acid.
DapagliflozinLipoic Acid may increase the hypoglycemic activities of Dapagliflozin.
DulaglutideLipoic Acid may increase the hypoglycemic activities of Dulaglutide.
EmpagliflozinLipoic Acid may increase the hypoglycemic activities of Empagliflozin.
ExenatideLipoic Acid may increase the hypoglycemic activities of Exenatide.
Ferric CitrateFerric Citrate can cause a decrease in the absorption of Lipoic Acid resulting in a reduced serum concentration and potentially a decrease in efficacy.
GliclazideLipoic Acid may increase the hypoglycemic activities of Gliclazide.
GlimepirideLipoic Acid may increase the hypoglycemic activities of Glimepiride.
GlipizideLipoic Acid may increase the hypoglycemic activities of Glipizide.
GlyburideLipoic Acid may increase the hypoglycemic activities of Glyburide.
Insulin AspartLipoic Acid may increase the hypoglycemic activities of Insulin Aspart.
Insulin DegludecLipoic Acid may increase the hypoglycemic activities of Insulin degludec.
Insulin DetemirLipoic Acid may increase the hypoglycemic activities of Insulin Detemir.
Insulin GlargineLipoic Acid may increase the hypoglycemic activities of Insulin Glargine.
Insulin GlulisineLipoic Acid may increase the hypoglycemic activities of Insulin Glulisine.
Insulin HumanLipoic Acid may increase the hypoglycemic activities of Insulin Regular.
Insulin LisproLipoic Acid may increase the hypoglycemic activities of Insulin Lispro.
LiraglutideLipoic Acid may increase the hypoglycemic activities of Liraglutide.
Magnesium chlorideMagnesium chloride can cause a decrease in the absorption of Lipoic Acid resulting in a reduced serum concentration and potentially a decrease in efficacy.
Magnesium citrateMagnesium citrate can cause a decrease in the absorption of Lipoic Acid resulting in a reduced serum concentration and potentially a decrease in efficacy.
Magnesium hydroxideMagnesium hydroxide can cause a decrease in the absorption of Lipoic Acid resulting in a reduced serum concentration and potentially a decrease in efficacy.
Magnesium oxideMagnesium oxide can cause a decrease in the absorption of Lipoic Acid resulting in a reduced serum concentration and potentially a decrease in efficacy.
Magnesium salicylateMagnesium salicylate can cause a decrease in the absorption of Lipoic Acid resulting in a reduced serum concentration and potentially a decrease in efficacy.
Magnesium SulfateMagnesium Sulfate can cause a decrease in the absorption of Lipoic Acid resulting in a reduced serum concentration and potentially a decrease in efficacy.
MetforminLipoic Acid may increase the hypoglycemic activities of Metformin.
MiglitolLipoic Acid may increase the hypoglycemic activities of Miglitol.
NateglinideLipoic Acid may increase the hypoglycemic activities of Nateglinide.
PioglitazoneLipoic Acid may increase the hypoglycemic activities of Pioglitazone.
PramlintideLipoic Acid may increase the hypoglycemic activities of Pramlintide.
RepaglinideLipoic Acid may increase the hypoglycemic activities of Repaglinide.
RosiglitazoneLipoic Acid may increase the hypoglycemic activities of Rosiglitazone.
SaxagliptinLipoic Acid may increase the hypoglycemic activities of Saxagliptin.
SitagliptinLipoic Acid may increase the hypoglycemic activities of Sitagliptin.
TolazamideLipoic Acid may increase the hypoglycemic activities of Tolazamide.
TolbutamideLipoic Acid may increase the hypoglycemic activities of Tolbutamide.
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Transferase activity, transferring acyl groups
Specific Function:
Catalyzes the transfer of the lipoyl group from lipoyl-AMP to the specific lysine residue of lipoyl domains of lipoate-dependent enzymes.
Gene Name:
LIPT1
Uniprot ID:
Q9Y234
Molecular Weight:
42478.8 Da
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:16246025 ]
  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:16043486 ]
  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:10473591 ]
  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:8617275 ]
  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:17570395 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Sodium-dependent multivitamin transmembrane transporter activity
Specific Function:
Transports pantothenate, biotin and lipoate in the presence of sodium.
Gene Name:
SLC5A6
Uniprot ID:
Q9Y289
Molecular Weight:
68641.27 Da
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:10334869 ]
  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:11955628 ]
  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:12214555 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Metal ion binding
Specific Function:
Catalyzes the radical-mediated insertion of two sulfur atoms into the C-6 and C-8 positions of the octanoyl moiety bound to the lipoyl domains of lipoate-dependent enzymes, thereby converting the octanoylated domains into lipoylated derivatives.
Gene Name:
LIAS
Uniprot ID:
O43766
Molecular Weight:
41910.695 Da
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:11389890 ]
  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:9808738 ]
  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:10403368 ]
  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:15225307 ]
  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:16246025 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, nad(p)h as one donor, and incorporation of one atom of oxygen
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:
76689.12 Da
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:16391466 ]
  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. doi: 10.1021/tx800281h. [PubMed:19548358 ]
  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. doi: 10.1124/dmd.108.023424. Epub 2008 Oct 6. [PubMed:18838505 ]
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Drug created on June 13, 2005 07:24 / Updated on May 01, 2016 15:14