ContaminantDB: (R)-lipoic acid

Identification Taxonomy Biological Properties Physical Properties Toxicity Profile Spectra Concentrations Links References Targets (6)XML

Record Information

Version

1.0

Creation Date

2009-07-21 20:26:12 UTC

Update Date

2026-04-05 11:18:38 UTC

Accession Number

CHEM002134

Identification

Common Name

(R)-lipoic acid

Class

Small Molecule

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.

Contaminant Sources

Cosmetic Chemicals
STOFF IDENT Compounds
T3DB toxins
ToxCast & Tox21 Chemicals

Contaminant Type

Animal Toxin
Antioxidant
Dietary Supplement
Drug
Household Toxin
Metabolite
Micronutrient
Natural Compound
Nutraceutical
Organic Compound
Plant Toxin
Supplement
Vitamin B Complex

Chemical Structure

MOL SDF 3D-SDF PDB SMILES InChI View 3D Structure

Synonyms

Value	Source
1,2-Dithiolane-3-pentanoic acid	ChEBI
1,2-Dithiolane-3-valeric acid	ChEBI
5-(1,2-Dithiolan-3-yl)valeric acid	ChEBI
5-(Dithiolan-3-yl)valeric acid	ChEBI
5-[3-(1,2-Dithiolanyl)]pentanoic acid	ChEBI
6,8-Thioctic acid	ChEBI
6,8-Thiotic acid	ChEBI
6-Thioctic acid	ChEBI
6-Thiotic acid	ChEBI
Acetate-replacing factor	ChEBI
alpha-Lipoic acid	ChEBI
alpha-Liponsaeure	ChEBI
Biletan	ChEBI
Liponic acid	ChEBI
Thioctansaeure	ChEBI
Thioctic acid	ChEBI
Thioctsaeure	ChEBI
Thioktsaeure	ChEBI
Thiotomin	Kegg
Lipoic acid	Kegg
DL-alpha-Lipoic acid	Kegg
DL-Thioctic acid	Kegg
1,2-Dithiolane-3-pentanoate	Generator
1,2-Dithiolane-3-valerate	Generator
5-(1,2-Dithiolan-3-yl)valerate	Generator
5-(Dithiolan-3-yl)valerate	Generator
5-[3-(1,2-Dithiolanyl)]pentanoate	Generator
6,8-Thioctate	Generator
6,8-Thiotate	Generator
6-Thioctate	Generator
6-Thiotate	Generator
Acetic acid-replacing factor	Generator
a-Lipoate	Generator
a-Lipoic acid	Generator
alpha-Lipoate	Generator
Α-lipoate	Generator
Α-lipoic acid	Generator
a-Liponsaeure	Generator
Α-liponsaeure	Generator
Liponate	Generator
Thioctate	Generator
DL-a-Lipoate	Generator
DL-a-Lipoic acid	Generator
DL-alpha-Lipoate	Generator
DL-Α-lipoate	Generator
DL-Α-lipoic acid	Generator
DL-Thioctate	Generator
Acid, alpha-lipoic	MeSH
Alpha Lipogamma	MeSH
Alpha Lipon stada	MeSH
Alpha Liponsaure sofotec	MeSH
Alpha Lippon al	MeSH
Alpha-Lipogamma	MeSH
Alpha-Lipon stada	MeSH
Alpha-Liponsaure sofotec	MeSH
Alpha-Lippon al	MeSH
AlphaLipogamma	MeSH
AlphaLipon stada	MeSH
AlphaLiponsaure sofotec	MeSH
AlphaLippon al	MeSH
Alphaflam	MeSH
Azulipont	MeSH
Fenint	MeSH
Injekt, thiogamma	MeSH
Juthiac	MeSH
Liponsaure ratiopharm	MeSH
Liponsaure-ratiopharm	MeSH
Liponsaureratiopharm	MeSH
MTW Alphaliponsaure	MeSH
MTW-Alphaliponsaure	MeSH
MTWAlphaliponsaure	MeSH
Neurium	MeSH
Pleomix Alpha	MeSH
Pleomix Alpha N	MeSH
Pleomix-Alpha	MeSH
Pleomix-Alpha N	MeSH
PleomixAlpha	MeSH
PleomixAlpha N	MeSH
Thioctacid	MeSH
Thioctacide T	MeSH
Thiogamma injekt	MeSH
Thiogamma oral	MeSH
Tromlipon	MeSH
Verla lipon	MeSH
Verla-lipon	MeSH
VerlaLipon	MeSH
alpha Lipoic acid	MeSH
alpha Liponaure heumann	MeSH
alpha Liponsaure von CT	MeSH
alpha Vibolex	MeSH
alpha-Liponaure heumann	MeSH
alpha-Liponsaure von CT	MeSH
alpha-Vibolex	MeSH
AlphaLiponaure heumann	MeSH
AlphaLiponsaure von CT	MeSH
AlphaVibolex	MeSH
Biomo lipon	MeSH
Biomo-lipon	MeSH
Biomolipon	MeSH
Duralipon	MeSH
Espa lipon	MeSH
Espa-lipon	MeSH
Espalipon	MeSH
(R)-Lipoate	Generator
Generosan brand OF thioctic acid	MeSH
Merck dura brand OF thioctic acid	MeSH
Rosen brand OF thioctic acid	MeSH
Trommsdorgg brand OF thioctic acid	MeSH
Viatris brand OF thioctic acid tromethamine	MeSH
Esparma brand OF thioctic acid	MeSH
Hexal brand OF thioctic acid	MeSH
Stadapharm brand OF thioctic acid	MeSH
Viatris brand OF thioctic acid	MeSH
Ratiopharm brand OF thioctic acid	MeSH
Aliud brand OF thioctic acid	MeSH
Illa brand OF thioctic acid	MeSH
Illa brand OF thioctic acid tromethamine	MeSH
MTW Brand OF thioctic acid	MeSH
Pharmacia brand OF thioctic acid	MeSH
Q Pharm brand OF thioctic acid	MeSH
Q-Pharm brand OF thioctic acid	MeSH
Azupharma brand OF thioctic acid	MeSH
Heumann brand OF thioctic acid	MeSH
Juta brand OF thioctic acid	MeSH
Lichtenstein brand OF thioctic acid	MeSH
Sofotec brand OF thioctic acid	MeSH
Verla brand OF thioctic acid	MeSH
Worwag brand OF thioctic acid	MeSH
Worwag brand OF thioctic acid meglumine	MeSH
biomo Brand OF thioctic acid	MeSH
CT Arzneimittel brand OF thioctic acid	MeSH
CT-Arzneimittel brand OF thioctic acid	MeSH

Chemical Formula

C₈H₁₄O₂S₂

Average Molecular Mass

206.326 g/mol

Monoisotopic Mass

206.044 g/mol

CAS Registry Number

62-46-4

IUPAC Name

5-(1,2-dithiolan-3-yl)pentanoic acid

Traditional Name

6,8-thioctic acid

SMILES

OC(=O)CCCCC1CCSS1

InChI Identifier

InChI=1S/C8H14O2S2/c9-8(10)4-2-1-3-7-5-6-11-12-7/h7H,1-6H2,(H,9,10)

InChI Key

AGBQKNBQESQNJD-UHFFFAOYSA-N

Chemical Taxonomy

Description

belongs to the class of organic compounds known as lipoic acids and derivatives. Lipoic acids and derivatives 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.

Kingdom

Organic compounds

Super Class

Organoheterocyclic compounds

Class

Dithiolanes

Sub Class

Lipoic acids and derivatives

Direct Parent

Lipoic acids and derivatives

Alternative Parents

Substituents

Lipoic_acid_derivative
Medium-chain fatty acid
Heterocyclic fatty acid
Thia fatty acid
Fatty acyl
Fatty acid
1,2-dithiolane
Organic disulfide
Monocarboxylic acid or derivatives
Carboxylic acid
Carboxylic acid derivative
Hydrocarbon derivative
Organooxygen compound
Organic oxide
Organic oxygen compound
Carbonyl group
Aliphatic heteromonocyclic compound

Molecular Framework

Aliphatic heteromonocyclic compounds

External Descriptors

dithiolanes (CHEBI:16494 )
thia fatty acid (CHEBI:16494 )
heterocyclic fatty acid (CHEBI:16494 )
Prosthetic group [Fig] (C00725 )

Biological Properties

Status

Detected and Not Quantified

Origin

Endogenous

Cellular Locations

Cytoplasm
Extracellular
Membrane

Biofluid Locations

Not Available

Tissue Locations

Kidney
Liver
Muscle
Nerve Cells
Placenta
Skeletal Muscle

Pathways

Name	SMPDB Link	KEGG Link
Ammonia Recycling	SMP00009	map00910
Glycine and Serine Metabolism	SMP00004	map00260

Applications

nutraceutical

Biological Roles

prosthetic group

Chemical Roles

Not Available

Physical Properties

State

Solid

Appearance

White powder.

Experimental Properties

Property	Value
Melting Point	60.5°C
Boiling Point	162.5°C
Solubility	Insoluble

Predicted Properties

Property	Value	Source
Water Solubility	0.22 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 Å²	ChemAxon
Rotatable Bond Count	5	ChemAxon
Refractivity	54.37 m³·mol⁻¹	ChemAxon
Polarizability	22 Å³	ChemAxon
Number of Rings	1	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	Yes	ChemAxon
MDDR-like Rule	No	ChemAxon

Spectra

Spectrum Type	Description	Splash Key	View
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	splash10-0udi-4900000000-59fc063b5aa5a8b5db19	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	Not Available	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_1_1) - 70eV, Positive	Not Available	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TBDMS_1_1) - 70eV, Positive	Not Available	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 10V, Negative	splash10-00di-0900000000-50da42c94591e9a60c0f	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 20V, Negative	splash10-004i-0900000000-1346e3a528dca0514cf7	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 90V, Negative	splash10-03di-9000000000-420a38a26d85b4091edb	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 75V, Negative	splash10-03di-9000000000-24b63eebe2fd067ce4b8	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 15V, Negative	splash10-0229-6900000000-44bcc93e18aeabd9ee16	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 30V, Negative	splash10-03k9-9600000000-4f680dfeae7fa1ece57a	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 45V, Negative	splash10-03di-9000000000-6f0b91016a33e202e49b	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 60V, Negative	splash10-03di-9000000000-e3d4a7fe022cf20db036	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-052r-0920000000-cf913d1d1afc04e5450c	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-0bti-5910000000-294c510229247ef63f20	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-0bvi-9600000000-f8f54eb79c5d4d5bef48	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-0a4i-0920000000-5a823a30dd1fb434e5b1	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-0kmu-1910000000-6f491a68afd82922e71b	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-0a4i-9200000000-330e4766f82ed571497b	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-0a4r-0970000000-0ae5b11a032d11c1ba6d	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-03di-1900000000-decf255617c1bbd69bfb	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-000i-6900000000-eb58a3d8135ba85d4283	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-0a4i-0190000000-014d2ea36cfae0726a9e	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-0a4i-5950000000-4e2dd5ccdcd5b0a936a0	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-0a59-9500000000-9bbbd7b252fb9a0b438d	Spectrum
1D NMR	1H NMR Spectrum	Not Available	Spectrum
1D NMR	13C NMR Spectrum	Not Available	Spectrum

Toxicity Profile

Route of Exposure

Not Available

Mechanism of Toxicity

(R)-lipoic acid is a cholinesterase or acetylcholinesterase (AChE) inhibitor. A cholinesterase inhibitor (or 'anticholinesterase') suppresses the action of acetylcholinesterase. Because of its essential function, chemicals that interfere with the action of acetylcholinesterase are potent neurotoxins, causing excessive salivation and eye-watering in low doses, followed by muscle spasms and ultimately death. Nerve gases and many substances used in insecticides have been shown to act by binding a serine in the active site of acetylcholine esterase, inhibiting the enzyme completely. Acetylcholine esterase breaks down the neurotransmitter acetylcholine, which is released at nerve and muscle junctions, in order to allow the muscle or organ to relax. The result of acetylcholine esterase inhibition is that acetylcholine builds up and continues to act so that any nerve impulses are continually transmitted and muscle contractions do not stop. Among the most common acetylcholinesterase inhibitors are phosphorus-based compounds, which are designed to bind to the active site of the enzyme. The structural requirements are a phosphorus atom bearing two lipophilic groups, a leaving group (such as a halide or thiocyanate), and a terminal oxygen.

Metabolism

Paraoxonase (PON1) is a key enzyme in the metabolism of organophosphates. PON1 can inactivate some organophosphates through hydrolysis. PON1 hydrolyzes the active metabolites in several organophosphates insecticides as well as, nerve agents such as soman, sarin, and VX. The presence of PON1 polymorphisms causes there to be different enzyme levels and catalytic efficiency of this esterase, which in turn suggests that different individuals may be more susceptible to the toxic effect of OP exposure.

Toxicity Values

Not Available

Lethal Dose

Not Available

Carcinogenicity (IARC Classification)

No indication of carcinogenicity to humans (not listed by IARC).

Uses/Sources

For nutritional supplementation, also for treating dietary shortage or imbalance.

Minimum Risk Level

Not Available

Health Effects

Acute exposure to cholinesterase inhibitors can cause a cholinergic crisis characterized by severe nausea/vomiting, salivation, sweating, bradycardia, hypotension, collapse, and convulsions. Increasing muscle weakness is a possibility and may result in death if respiratory muscles are involved. Accumulation of ACh at motor nerves causes overstimulation of nicotinic expression at the neuromuscular junction. When this occurs symptoms such as muscle weakness, fatigue, muscle cramps, fasciculation, and paralysis can be seen. When there is an accumulation of ACh at autonomic ganglia this causes overstimulation of nicotinic expression in the sympathetic system. Symptoms associated with this are hypertension, and hypoglycemia. Overstimulation of nicotinic acetylcholine receptors in the central nervous system, due to accumulation of ACh, results in anxiety, headache, convulsions, ataxia, depression of respiration and circulation, tremor, general weakness, and potentially coma. When there is expression of muscarinic overstimulation due to excess acetylcholine at muscarinic acetylcholine receptors symptoms of visual disturbances, tightness in chest, wheezing due to bronchoconstriction, increased bronchial secretions, increased salivation, lacrimation, sweating, peristalsis, and urination can occur. Certain reproductive effects in fertility, growth, and development for males and females have been linked specifically to organophosphate pesticide exposure. Most of the research on reproductive effects has been conducted on farmers working with pesticides and insecticdes in rural areas. In females menstrual cycle disturbances, longer pregnancies, spontaneous abortions, stillbirths, and some developmental effects in offspring have been linked to organophosphate pesticide exposure. Prenatal exposure has been linked to impaired fetal growth and development. Neurotoxic effects have also been linked to poisoning with OP pesticides causing four neurotoxic effects in humans: cholinergic syndrome, intermediate syndrome, organophosphate-induced delayed polyneuropathy (OPIDP), and chronic organophosphate-induced neuropsychiatric disorder (COPIND). These syndromes result after acute and chronic exposure to OP pesticides.

Symptoms

Symptoms of low dose exposure include excessive salivation and eye-watering. Acute dose symptoms include severe nausea/vomiting, salivation, sweating, bradycardia, hypotension, collapse, and convulsions. Increasing muscle weakness is a possibility and may result in death if respiratory muscles are involved. Hypertension, hypoglycemia, anxiety, headache, tremor and ataxia may also result.

Treatment

If the compound has been ingested, rapid gastric lavage should be performed using 5% sodium bicarbonate. For skin contact, the skin should be washed with soap and water. If the compound has entered the eyes, they should be washed with large quantities of isotonic saline or water. In serious cases, atropine and/or pralidoxime should be administered. Anti-cholinergic drugs work to counteract the effects of excess acetylcholine and reactivate AChE. Atropine can be used as an antidote in conjunction with pralidoxime or other pyridinium oximes (such as trimedoxime or obidoxime), though the use of '-oximes' has been found to be of no benefit, or possibly harmful, in at least two meta-analyses. Atropine is a muscarinic antagonist, and thus blocks the action of acetylcholine peripherally.

Concentrations

Not Available

External Links

DrugBank ID

Not Available

HMDB ID

HMDB0251530

FooDB ID

FDB004339

Phenol Explorer ID

Not Available

KNApSAcK ID

C00041416

BiGG ID

Not Available

BioCyc ID

Not Available

METLIN ID

Not Available

PDB ID

Not Available

Wikipedia Link

Chemspider ID

ChEBI ID

PubChem Compound ID

Kegg Compound ID

YMDB ID

Not Available

ECMDB ID

ECMDB23028

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.

MSDS

Link

General References

1. https://www.ncbi.nlm.nih.gov/pubmed/?term=7519986

2. https://www.ncbi.nlm.nih.gov/pubmed/?term=7548757

(R)-lipoic acid (CHEM002134)

Structure for CHEM002134: (R)-lipoic acid