| Record Information |
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| Version | 2.0 |
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| Creation Date | 2009-07-21 20:26:12 UTC |
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| Update Date | 2014-12-24 20:25:49 UTC |
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| Accession Number | T3D2702 |
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| Identification |
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| Common Name | (R)-lipoic acid |
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| Class | Small Molecule |
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| 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. |
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| Compound Type | - Animal Toxin
- Antioxidant
- Dietary Supplement
- Drug
- Household Toxin
- Metabolite
- Micronutrient
- Natural Compound
- Nutraceutical
- Organic Compound
- Plant Toxin
- Supplement
- Vitamin B Complex
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| Chemical Structure | |
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| Synonyms | | Synonym | | (+)-alpha-Lipoic acid | | (R)-(+)-lipoic acid | | (R)-1,2-Dithiolane-3-pentanoic acid | | (R)-1,2-dithiolane-3-valeric acid | | (R)-6,8-thioctic acid | | (R)-Lipoate | | (R)-Lipoic acid | | 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 | | 6,8-thioctic acid | | 6,8-thiotic acid | | 6-thioctic acid | | 6-thiotic acid | | Acetate-replacing factor | | alpha-Lipoic acid | | alpha-Liponsaeure | | Biletan | | Lipoic acid | | liponic acid | | R-LA | | RLA | | Thioctansaeure | | Thioctic acid | | Thioctic acid d-form | | Thioctsaeure | | Thioktsaeure | | α-lipoic acid |
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| Chemical Formula | C8H14O2S2 |
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| Average Molecular Mass | 206.326 g/mol |
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| Monoisotopic Mass | 206.044 g/mol |
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| CAS Registry Number | 62-46-4 |
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| IUPAC Name | 5-(1,2-dithiolan-3-yl)pentanoic acid |
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| Traditional Name | 6,8-thioctic acid |
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| SMILES | OC(=O)CCCCC1CCSS1 |
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| InChI Identifier | InChI=1/C8H14O2S2/c9-8(10)4-2-1-3-7-5-6-11-12-7/h7H,1-6H2,(H,9,10) |
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| InChI Key | InChIKey=AGBQKNBQESQNJD-UHFFFAOYNA-N |
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| Chemical Taxonomy |
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| 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. |
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| Kingdom | Organic compounds |
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| Super Class | Organoheterocyclic compounds |
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| Class | Dithiolanes |
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| Sub Class | Lipoic acids and derivatives |
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| Direct Parent | Lipoic acids and derivatives |
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| Alternative Parents | |
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| 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
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| Molecular Framework | Aliphatic heteromonocyclic compounds |
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| External Descriptors | |
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| Biological Properties |
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| Status | Detected and Not Quantified |
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| Origin | Endogenous |
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| Cellular Locations | - Cytoplasm
- Extracellular
- Membrane
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| Biofluid Locations | Not Available |
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| Tissue Locations | - Kidney
- Liver
- Muscle
- Nerve Cells
- Placenta
- Skeletal Muscle
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| Pathways | |
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| Applications | |
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| Biological Roles | |
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| Chemical Roles | Not Available |
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| Physical Properties |
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| State | Solid |
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| Appearance | White powder. |
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| Experimental Properties | | Property | Value |
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| Melting Point | 60.5°C | | Boiling Point | 162.5°C | | Solubility | Insoluble | | LogP | 2.1 |
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| Predicted Properties | |
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| Spectra |
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| Spectra | | Spectrum Type | Description | Splash Key | Deposition Date | View |
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| Predicted GC-MS | Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive | splash10-0udi-4900000000-59fc063b5aa5a8b5db19 | 2021-09-24 | View Spectrum | | Predicted GC-MS | Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive | Not Available | 2021-10-12 | View Spectrum | | Predicted GC-MS | Predicted GC-MS Spectrum - GC-MS (TMS_1_1) - 70eV, Positive | Not Available | 2021-11-04 | View Spectrum | | Predicted GC-MS | Predicted GC-MS Spectrum - GC-MS (TBDMS_1_1) - 70eV, Positive | Not Available | 2021-11-04 | View Spectrum | | LC-MS/MS | LC-MS/MS Spectrum - 10V, Negative | splash10-00di-0900000000-50da42c94591e9a60c0f | 2021-09-20 | View Spectrum | | LC-MS/MS | LC-MS/MS Spectrum - 20V, Negative | splash10-004i-0900000000-1346e3a528dca0514cf7 | 2021-09-20 | View Spectrum | | LC-MS/MS | LC-MS/MS Spectrum - 90V, Negative | splash10-03di-9000000000-420a38a26d85b4091edb | 2021-09-20 | View Spectrum | | LC-MS/MS | LC-MS/MS Spectrum - 75V, Negative | splash10-03di-9000000000-24b63eebe2fd067ce4b8 | 2021-09-20 | View Spectrum | | LC-MS/MS | LC-MS/MS Spectrum - 15V, Negative | splash10-0229-6900000000-44bcc93e18aeabd9ee16 | 2021-09-20 | View Spectrum | | LC-MS/MS | LC-MS/MS Spectrum - 30V, Negative | splash10-03k9-9600000000-4f680dfeae7fa1ece57a | 2021-09-20 | View Spectrum | | LC-MS/MS | LC-MS/MS Spectrum - 45V, Negative | splash10-03di-9000000000-6f0b91016a33e202e49b | 2021-09-20 | View Spectrum | | LC-MS/MS | LC-MS/MS Spectrum - 60V, Negative | splash10-03di-9000000000-e3d4a7fe022cf20db036 | 2021-09-20 | View Spectrum | | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 10V, Positive | splash10-052r-0920000000-cf913d1d1afc04e5450c | 2015-09-15 | View Spectrum | | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 20V, Positive | splash10-0bti-5910000000-294c510229247ef63f20 | 2015-09-15 | View Spectrum | | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 40V, Positive | splash10-0bvi-9600000000-f8f54eb79c5d4d5bef48 | 2015-09-15 | View Spectrum | | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 10V, Negative | splash10-0a4i-0920000000-5a823a30dd1fb434e5b1 | 2015-09-15 | View Spectrum | | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 20V, Negative | splash10-0kmu-1910000000-6f491a68afd82922e71b | 2015-09-15 | View Spectrum | | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 40V, Negative | splash10-0a4i-9200000000-330e4766f82ed571497b | 2015-09-15 | View Spectrum | | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 10V, Positive | splash10-0a4r-0970000000-0ae5b11a032d11c1ba6d | 2021-10-12 | View Spectrum | | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 20V, Positive | splash10-03di-1900000000-decf255617c1bbd69bfb | 2021-10-12 | View Spectrum | | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 40V, Positive | splash10-000i-6900000000-eb58a3d8135ba85d4283 | 2021-10-12 | View Spectrum | | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 10V, Negative | splash10-0a4i-0190000000-014d2ea36cfae0726a9e | 2021-10-12 | View Spectrum | | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 20V, Negative | splash10-0a4i-5950000000-4e2dd5ccdcd5b0a936a0 | 2021-10-12 | View Spectrum | | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 40V, Negative | splash10-0a59-9500000000-9bbbd7b252fb9a0b438d | 2021-10-12 | View Spectrum | | 1D NMR | 1H NMR Spectrum (1D, 400 MHz, CDCl3, experimental) | Not Available | 2016-09-22 | View Spectrum | | 1D NMR | 13C NMR Spectrum (1D, 25.16 MHz, CDCl3, experimental) | Not Available | 2016-09-22 | View Spectrum |
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| Toxicity Profile |
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| Route of Exposure | Not Available |
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| 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. |
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| 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. |
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| Toxicity Values | Not Available |
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| Lethal Dose | Not Available |
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| Carcinogenicity (IARC Classification) | No indication of carcinogenicity to humans (not listed by IARC). |
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| Uses/Sources | For nutritional supplementation, also for treating dietary shortage or imbalance. |
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| Minimum Risk Level | Not Available |
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| 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. |
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| 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. |
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| 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. |
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| Normal Concentrations |
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| Not Available |
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| Abnormal Concentrations |
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| Not Available |
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| External Links |
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| DrugBank ID | DB00166 |
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| HMDB ID | HMDB01451 |
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| PubChem Compound ID | 6112 |
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| ChEMBL ID | CHEMBL134342 |
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| ChemSpider ID | 5886 |
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| KEGG ID | C00725 |
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| UniProt ID | Not Available |
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| OMIM ID | |
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| ChEBI ID | 16494 |
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| BioCyc ID | LIPOIC-ACID |
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| CTD ID | Not Available |
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| Stitch ID | Lipoic Acid |
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| PDB ID | LPA |
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| ACToR ID | Not Available |
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| Wikipedia Link | Lipoic_Acid |
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| References |
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| 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. |
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| MSDS | Link |
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| General References | - Perham RN: Swinging arms and swinging domains in multifunctional enzymes: catalytic machines for multistep reactions. Annu Rev Biochem. 2000;69:961-1004. [10966480 ]
- 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. [14854913 ]
- 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. [12715971 ]
- 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. [8769129 ]
- 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. [2509239 ]
- 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. [9741583 ]
- 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. [15998258 ]
- 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. [14724823 ]
- 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. [10370185 ]
- Tankova T, Cherninkova S, Koev D: Treatment for diabetic mononeuropathy with alpha-lipoic acid. Int J Clin Pract. 2005 Jun;59(6):645-50. [15924591 ]
- 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. [9063572 ]
- 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. [7595680 ]
- 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. [14669930 ]
- 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. [15703366 ]
- 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. [10722093 ]
- 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. [7587852 ]
- Steinmann B, Gitzelmann R: Strychnine treatment attempted in newborn twins with severe nonketotic hyperglycinemia. Helv Paediatr Acta. 1979;34(6):589-99. [541222 ]
- 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. [16224049 ]
- McCormick DB: A trail of research on cofactors: an odyssey with friends. J Nutr. 2000 Feb;130(2S Suppl):323S-330S. [10721897 ]
- 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. [8160293 ]
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| Gene Regulation |
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| Up-Regulated Genes | | Gene | Gene Symbol | Gene ID | Interaction | Chromosome | Details |
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| Down-Regulated Genes | Not Available |
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