Lipoic acid

Structural formula
	Simplified structural formula (without stereochemistry )
General
Surname	Lipoic acid
other names	Thioctic acid; 1,2-dithiolane-3-pentanoic acid; 5 - [(3 RS ) -1,2-dithiolan-3-yl] pentanoic acid ( IUPAC );
Molecular formula	C 8 H 14 O 2 S 2
Brief description	yellowish needles [( RS ) lipoic acid]
External identifiers / databases
EC number	214-071-2
ECHA InfoCard	100.012.793
PubChem	864
ChemSpider	841
Wikidata	Q312229
Drug information
ATC code	A16 AX01 ; N07 XB52 ;
Drug class	Neuropathic drugs
properties
Molar mass	206.33 g · mol -1
Physical state	firmly
Melting point	60–61 ° C [( RS ) lipoic acid]; 46–48 ° C [( R ) -lipoic acid];
boiling point	160–165 ° C [( R ) -lipoic acid]
pK s value	5.4
solubility	almost insoluble in water (127 mg l −1 at 25 ° C), poor in ethanol (50 g l −1 )
safety instructions
	Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS labeling of hazardous substances Caution
H and P phrases	H: 302
	P: no P-phrases
Toxicological data	502 mg kg −1 ( LD 50 , mouse , oral )
	As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Alpha lipoic acid , (abbreviated LA from the English lipoic acid or ALA from the English alpha lipoic acid ; other name thioctic acid ) is a sulfur-containing fatty acid . In its natural ( R ) form, it occurs as a coenzyme in the mitochondria of almost all eukaryotes and plays an important role in energy metabolism. The salts of lipoic acid are called lipoates .

Structure and isomerism

Alpha-lipoic acid is a sulfur-containing fatty acid, the two sulfur atoms being linked together in a ring structure. The natural α-lipoic acid is ( R ) -configured at the (single) stereogenic center ; their enantiomer is ( S ) -configured.

Isomers of lipoic acid
Surname	( R ) lipoic acid	( S ) -lipoic acid
other names	L -lipoic acid (+) - lipoic acid	D -lipoic acid (-) - lipoic acid
Structural formula
CAS number	1200-22-2	1077-27-6
	1077-28-7 ( RS )
EC number	638-752-2	664-251-3
	214-071-2 (unspec.)
ECHA info card	100.166.365	100.190.488
	100.012.793 (unspec.)
PubChem	6112	445125
	864 (unspec.)
DrugBank	DB00166	-
Wikidata	Q27887203	Q21097956
	Q312229 (unspec.)

In nature, only ( R ) -lipoic acid (synonym L -lipoic acid) and its reduced form, dihydrolipoic acid (6,8-dithiooctanoic acid), are biologically active. Structural analogues with six- or more-membered rings are biologically inactive.

In addition to ( R ) -lipoic acid, the racemate ( RS ) -lipoic acid [synonyms: DL -lipoic acid, (±) -lipoic acid] is also used as a medicinal substance .

function

α-Lipoic acid acts as a coenzyme in many enzymatic reactions, primarily in oxidative decarboxylation . Their task is to transfer hydrogen and acyl groups. As part of the pyruvate dehydrogenase complex of the mitochondria , the link between glycolysis and the citric acid cycle and the α-ketoglutarate dehydrogenase complex in the citric acid cycle, it plays an important role in the energy metabolism. With its reduced form, dihydrolipoic acid, α-lipoic acid forms a biochemical redox system. Alpha-lipoic acid is a radical scavenger and powerful antioxidant that can regenerate antioxidants such as vitamin C , vitamin E , coenzyme Q10 or glutathione that are used up in the body .

α- Lipoic acid also acts as an antidote for poisoning with Amanita mushrooms.

use

α-Lipoic acid has been used in Germany as a medicinal substance for the treatment of liver diseases and peripheral polyneuropathies since 1966 .

In chelation therapy , α-lipoic acid can be used in the event of poisoning with inorganic mercury compounds . In contrast to other chelating agents such as DMSA or DMPS , lipoic acid can penetrate all areas of the central and peripheral nervous system, in particular it can cross the blood-brain barrier . Their effectiveness for this purpose is based primarily on their reduced form, dihydrolipoic acid , a dithiol that has strong antioxidant properties and can form chelate bonds. These complexes are excreted almost exclusively via the biliary tract.

Because of its antioxidant effect, α-lipoic acid is also offered as a dietary supplement .

Trade names

Monopreparations

Alpha-Lipogamma (D), Alpha-Lipon STADA (D), Alpha-Vibolex (D), Biomo-Lipon (D), espa-lipon (D), Liponsäure-ratiopharm (D), Neurium (D), Pleomix- Alpha (D), Sana Alpha-Lipoic Acid (D), Thioctacid (D, A), Thiogamma (D), Tromlipon (D), Vitatrans (D), Alpha-Lipon AL (D), Alpan (D), Unilipon ( D).

literature

Biewenga, GP. et al. (1997): The Pharmacology of the Antioxidant Lipoic Acid. In: Gen Pharmacol . 29 (3); 315-331; PMID 9378235 .
Biewenga, GP. et al. (1997): The role of lipoic acid in the treatment of diabetic polyneuropathy. In: Drug Metab Rev . 29 (4), 1025-1054; PMID 9421684 .
Berkson Burt (1998): The Alpha Lipoic Acid Breakthrough. Three Rivers Press New York; ISBN 0-7615-1457-0 .

Individual evidence

↑ ^a ^b ^c Entry on lipoic acid. In: Römpp Online . Georg Thieme Verlag, accessed on April 17, 2013.
↑ ^a ^b ^c The Merck Index , 9th Edition, 1976, ISBN 0-911910-26-3 ; Pp. 1203-1204.
↑ ^a ^b Entry on lipoic acid in the ChemIDplus database of the United States National Library of Medicine (NLM) .
↑ ^a ^b ^c data sheet (±) -α-Lipoic acid from Sigma-Aldrich , accessed on April 7, 2011 ( PDF ).
↑ Peter Nuhn: Naturstoffchemie , S. Hirzel Wissenschaftliche Verlagsgesellschaft Stuttgart, 1990, ISBN 3-7776-0473-9 , p. 359.
↑ External identifiers or database links for dihydrolipoic acid: CAS number: 462-20-4, EC number: 610-288-5, ECHA InfoCard: 100.120.390 , PubChem : 421 , ChemSpider : 408 , DrugBank : DB03760 , Wikidata : Q5276437 .
↑ A. Gorąca, H. Huk-Kolega et al. a .: Lipoic acid - biological activity and therapeutic potential. In: Pharmacological Reports Volume 63, Number 4, 2011, pp. 849-858, PMID 22001972 .
↑ Frank D. Gunstone, John L. Harwood, Albert J. Dijkstra: The Lipid Handbook. Third Edition, CRC Press, 2007, ISBN 0-8493-9688-3 , p. 12.
^ Rooney J: The role of thiols, dithiols, nutritional factors and interacting ligands in the toxicology of mercury . In: Toxicology . 234, No. 3, 2007, pp. 145-156. doi : 10.1016 / j.tox.2007.02.016 . PMID 17408840 .
↑ Packer L, Tritschler HJ, Wessel K: Neuroprotection by the metabolic antioxidant alpha-lipoic acid . In: Free Radical Biology and Medicine . 22, No. 1-2, 1997, pp. 359-378. PMID 8958163 .
↑ Gregus Z, Stein AF, Varga F, Klaassen CD: Effect of lipoic acid on biliary excretion of glutathione and metals . In: Toxicology and Applied Pharmacology . 114, No. 1, 1992, pp. 88-96. doi : 10.1016 / 0041-008X (92) 90100-7 . PMID 1585376 .

[roempp-1] Entry on lipoic acid. In: Römpp Online . Georg Thieme Verlag, accessed on April 17, 2013.

[Merck-2] The Merck Index , 9th Edition, 1976, ISBN 0-911910-26-3 ; Pp. 1203-1204.

[ChemIDplus-3] Entry on lipoic acid in the ChemIDplus database of the United States National Library of Medicine (NLM) .

[sigma-4] ta sheet (±) -α-Lipoic acid from Sigma-Aldrich , accessed on April 7, 2011 ( PDF ).

[Nuhn-5] Peter Nuhn: Naturstoffchemie , S. Hirzel Wissenschaftliche Verlagsgesellschaft Stuttgart, 1990, ISBN 3-7776-0473-9 , p. 359.

[6] External identifiers or database links for dihydrolipoic acid: CAS number: 462-20-4, EC number: 610-288-5, ECHA InfoCard: 100.120.390 , PubChem : 421 , ChemSpider : 408 , DrugBank : DB03760 , Wikidata : Q5276437 .

[PMID22001972-7] A. Gorąca, H. Huk-Kolega et al. a .: Lipoic acid - biological activity and therapeutic potential. In: Pharmacological Reports Volume 63, Number 4, 2011, pp. 849-858, PMID 22001972 .

[8] Frank D. Gunstone, John L. Harwood, Albert J. Dijkstra: The Lipid Handbook. Third Edition, CRC Press, 2007, ISBN 0-8493-9688-3 , p. 12.

[9] Rooney J: The role of thiols, dithiols, nutritional factors and interacting ligands in the toxicology of mercury . In: Toxicology . 234, No. 3, 2007, pp. 145-156. doi : 10.1016 / j.tox.2007.02.016 . PMID 17408840 .

[10] Packer L, Tritschler HJ, Wessel K: Neuroprotection by the metabolic antioxidant alpha-lipoic acid . In: Free Radical Biology and Medicine . 22, No. 1-2, 1997, pp. 359-378. PMID 8958163 .

[11] Gregus Z, Stein AF, Varga F, Klaassen CD: Effect of lipoic acid on biliary excretion of glutathione and metals . In: Toxicology and Applied Pharmacology . 114, No. 1, 1992, pp. 88-96. doi : 10.1016 / 0041-008X (92) 90100-7 . PMID 1585376 .