2.0 2012-05-31 13:52:59 -0600 2015-09-13 12:56:11 -0600 ECMDB01451 M2MDB000392 Lipoic acid Lipoic acid is a vitamin-like antioxidant that acts as a free-radical scavenger. Alpha-lipoic acid is also known as thioctic acid. 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. 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. (Wikipedia) &alpha;-liponate &alpha;-liponic acid (+)-a-Lipoate (+)-a-Lipoic acid (+)-alpha-Lipoate (+)-alpha-Lipoic acid (+)-α-Lipoate (+)-α-Lipoic acid (+-)-1,2-Dithiolane-3-pentanoate (+-)-1,2-Dithiolane-3-pentanoic acid (+-)-1,2-Dithiolane-3-valerate (+-)-1,2-Dithiolane-3-valeric acid (R)-1,2-Dithiolane-3-pentanoate (R)-1,2-Dithiolane-3-pentanoic acid (RS)-a-Lipoate (RS)-a-Lipoic acid (RS)-alpha-Lipoate (RS)-alpha-Lipoic acid (RS)-Lipoate (RS)-Lipoic acid (RS)-α-Lipoate (RS)-α-Lipoic acid 1,2-Dithiolane-3-pentanoate 1,2-Dithiolane-3-pentanoic acid 1,2-Dithiolane-3-valerate 1,2-Dithiolane-3-valeric acid 1,2-Dithiolane-3R-pentanoate 1,2-Dithiolane-3R-pentanoic acid 5-(1,2-Dithiolan-3-yl)-pentanoate 5-(1,2-Dithiolan-3-yl)-pentanoic acid 5-(1,2-Dithiolan-3-yl)pentanoate 5-(1,2-Dithiolan-3-yl)pentanoic acid 5-(1,2-Dithiolan-3-yl)valerate 5-(1,2-Dithiolan-3-yl)valeric acid 5-(Dithiolan-3-yl)valerate 5-(Dithiolan-3-yl)valeric acid 5-[3-(1,2-Dithiolanyl)]pentanoate 5-[3-(1,2-Dithiolanyl)]pentanoic acid 6,8-Dithiooctanoate 6,8-Dithiooctanoic acid 6,8-Thioctate 6,8-Thioctic acid 6,8-Thiotate 6,8-Thiotic acid 6-Thioctate 6-Thioctic acid 6-Thiotate 6-Thiotic acid a Lipoate a Lipoic acid a-Lipoate a-Lipoic acid a-Liponate a-Liponic acid a-Liponsaeure Acetate replacing factor Acetate-replacing factor Acetic acid replacing factor Acetic acid-replacing factor Alpha Lipoate Alpha Lipoic acid Alpha-Lipoate Alpha-Lipoic acid Alpha-Liponate Alpha-Liponic acid Alpha-Liponsaeure Biletan Delta-[3-(1,2-Dithiacyclopentyl)]pentanoate Delta-[3-(1,2-Dithiacyclopentyl)]pentanoic acid DL-1,2-Dithiolane 3-valerate DL-1,2-Dithiolane 3-valeric acid DL-6,8-Dithiooctanoate DL-6,8-Dithiooctanoic acid DL-6,8-Thioctate DL-6,8-Thioctic acid DL-6-Thioctate DL-6-Thioctic acid DL-a-Lipoate DL-a-Lipoic acid DL-alpha-Lipoate DL-alpha-Lipoic acid Dl-Lipoate Dl-Lipoic acid Dl-Thioctate DL-Thioctate > 98% Dl-Thioctic acid DL-Thioctic acid > 98% DL-α-Lipoate DL-α-Lipoic acid Heparlipon Lip Lipoate Lipoic acid Liponate Liponic acid Liposan Lipothion Protogen A Pyruvate oxidation factor Pyruvic acid oxidation factor R-Lipoate R-Lipoic acid Rac-lipoate Rac-lipoic acid Thioctacid Thioctan Thioctate Thioctate D-form Thioctate dl-form Thioctic acid Thioctic acid D-form Thioctic acid dl-form Thioctidase Thioctsan Thioktsaeure Thiooctanoate Thiooctanoic acid Tioctacid Tioctan Tioctidasi Tioctidasi acetate replacing factor Tioctidasi acetic acid replacing factor α Lipoate α Lipoic acid α-Lipoate α-Lipoic acid α-Liponate α-Liponic acid α-Liponsaeure δ-[3-(1,2-Dithiacyclopentyl)]pentanoate δ-[3-(1,2-Dithiacyclopentyl)]pentanoic acid C8H14O2S2 206.326 206.043521072 5-[(3R)-1,2-dithiolan-3-yl]pentanoic acid lipoic acid 1077-28-7 OC(=O)CCCC[C@@H]1CCSS1 InChI=1S/C8H14O2S2/c9-8(10)4-2-1-3-7-5-6-11-12-7/h7H,1-6H2,(H,9,10)/t7-/m1/s1 AGBQKNBQESQNJD-SSDOTTSWSA-N Solid Cytosol Extra-organism Membrane Periplasm logp 2.75 ALOGPS logs -2.96 ALOGPS solubility 2.24e-01 g/l ALOGPS melting_point 60.5 oC logp 2.11 ChemAxon pka_strongest_acidic 4.52 ChemAxon iupac 5-[(3R)-1,2-dithiolan-3-yl]pentanoic acid ChemAxon average_mass 206.326 ChemAxon mono_mass 206.043521072 ChemAxon smiles OC(=O)CCCC[C@@H]1CCSS1 ChemAxon formula C8H14O2S2 ChemAxon inchi InChI=1S/C8H14O2S2/c9-8(10)4-2-1-3-7-5-6-11-12-7/h7H,1-6H2,(H,9,10)/t7-/m1/s1 ChemAxon inchikey AGBQKNBQESQNJD-SSDOTTSWSA-N ChemAxon polar_surface_area 37.3 ChemAxon refractivity 54.37 ChemAxon polarizability 21.74 ChemAxon rotatable_bond_count 5 ChemAxon acceptor_count 2 ChemAxon donor_count 1 ChemAxon physiological_charge -1 ChemAxon formal_charge 0 ChemAxon Lipoic acid metabolism Lipoic acid metabolism starts with caprylic acid being introduced into the cytoplasm however no transporter has been identified yet. Once caprylic acid is in the cytoplasm, it can either reacts with a holo-acp, through an ATP driven 2-acylglycerophosphoethanolamine acyltransferase / acyl-ACP synthetase resulting in pyrophosphate, AMP and octanoyl-[acp]. The latter compound can also be obtained from palmitate biosynthesis. Octanoyl-acp interacts with a lipoyl-carrier protein L-lysine through a Octanoyltransferase resulting in a hydrogen ion, a holo-acyl-acp, and a protein N6-0octanoyl) lysine. The latter compound reacts with an S-adenosylmethionine, a sulfurated[sulfur carrier] and a reduced ferredoxin through a lipoate-protein ligase A, resulting in a 5-deoxyadenosine, a L-methionine, an unsulfurated [sulfur carrier], oxidized ferredoxin, and a Protein N6-(lipoyl) lysine. Caprylic acid can also interact with ATP and a lipoyl-carrier protein-L-lysine through a lipoate-protein ligase A resulting in a amp, pyrophosphate, hydrogen ion, protein N6-(octanoyl)lysine. The latter compound reacts with an S-adenosylmethionine, a sulfurated[sulfur carrier] and a reduced ferredoxin through a lipoate-protein ligase A, resulting in a 5-deoxyadenosine, a L-methionine, an unsulfurated [sulfur carrier], oxidized ferredoxin, and a Protein N6-(lipoyl) lysine. R-lipoic acid can be absorbed from the environment, as seen in studies by Morris TW. In this pathway the lipoyl-protein ligase LplA utilizes pre-existing lipoate that has been imported from outside the cell, and thus catalyzes a salvage pathway. Lipoic acid interacts with ATP and hydrogen ion through a lipoyl-protein ligase A, resulting in a pyrophosphate and a Lipoyl-AMP (lipoyl-adenylate). This compound then interacts with a lipoyl-carrier protein-L-lysine through a lipoate-protein ligase A resulting a AMP, a hydrogen ion and a Protein N6-(lipoyl) lysine. It has been suggested that the conversion of octanoylated-domains to lipoylated ones described in this pathway may be a type of a repair pathway, activated only if the other lipoate biosynthetic pathways are malfunctioning . PW000770 ec00785 Metabolic lipoate salvage I PWY0-522 Specdb::CMs 3089 Specdb::CMs 31800 Specdb::CMs 38079 Specdb::CMs 99686 Specdb::CMs 100076 Specdb::CMs 100077 Specdb::CMs 155727 Specdb::NmrOneD 1710 Specdb::MsMs 1580 Specdb::MsMs 1581 Specdb::MsMs 1582 Specdb::MsMs 179469 Specdb::MsMs 179470 Specdb::MsMs 179471 Specdb::MsMs 181797 Specdb::MsMs 181798 Specdb::MsMs 181799 Specdb::MsMs 2236189 Specdb::MsMs 2237205 Specdb::MsMs 2238327 Specdb::MsMs 2239242 Specdb::MsMs 2308539 Specdb::MsMs 2308540 Specdb::MsMs 2308541 Specdb::MsMs 2654048 Specdb::MsMs 2654049 Specdb::MsMs 2654050 Specdb::NmrTwoD 1651 HMDB01451 864 5886 C16241 16494 LIPOIC-ACID LPA Lipoic acid Keseler, I. 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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 http://hmdb.ca/system/metabolites/msds/000/001/313/original/HMDB01451.pdf?1358462814 Lipoate-protein ligase A P32099 LPLA_ECOLI lplA http://ecmdb.ca/proteins/P32099.xml Outer membrane protein N P77747 OMPN_ECOLI ompN http://ecmdb.ca/proteins/P77747.xml Outer membrane pore protein E P02932 PHOE_ECOLI phoE http://ecmdb.ca/proteins/P02932.xml Outer membrane protein F P02931 OMPF_ECOLI ompF http://ecmdb.ca/proteins/P02931.xml Outer membrane protein C P06996 OMPC_ECOLI ompC http://ecmdb.ca/proteins/P06996.xml Adenosine triphosphate + Lipoic acid > Lipoyl-AMP + Pyrophosphate R07770 RXN-8654 Adenosine triphosphate + Lipoic acid <> Pyrophosphate + Lipoyl-AMP R07770 Hydrogen ion + Lipoic acid + Adenosine triphosphate > Lipoyl-AMP + Pyrophosphate RXN-8654 (R)-lipoic acid + Adenosine triphosphate + Hydrogen ion + Lipoic acid > Pyrophosphate + Lipoyl-AMP + Lipoyl-AMP PW_R003559