2.02012-05-31 10:26:52 -06002015-10-02 02:25:50 -0600ECMDB00482M2MDB000140Caprylic acidCaprylic acid belongs to the class of Straight Chain Fatty Acids. These are fatty acids with a straight aliphatic chain. (inferred from compound structure). Caprylic acid is the common name for the eight-carbon saturated fatty acid known by the systematic name octanoic acid. (WikiPedia). Caprylic acid is an intermediate in lipoate biosynthesis and incorporation II in E. coli. It is a substrate for lipoate-protein ligase A which catalyzes the chemical reaction a [lipoyl-carrier protein]-L-lysine + caprylic acid + ATP -> a [lipoyl-carrier protein] N6-octanoyl-L-lysine + AMP + diphosphate + H+. It is also a substrate for acyl-ACP synthetase in the reaction caprylic acid + a holo-[acyl-carrier protein] + ATP → an octanoyl-[acp] + AMP + diphosphate (EcoCyc compound: CPD-195).1-Heptanecarboxylate1-Heptanecarboxylic acidC-8 AcidCaprylateCaprylic acidCapryloateCapryloic acidEmery 657Kortacid 0899Lunac 8-95Lunac 8-98N-CaprylateN-Caprylic acidN-OctanoateN-Octanoic acidN-OctateN-Octic acidN-OctoateN-Octoic acidN-OctylateN-Octylic acidNeo-Fat 8Neo-Fat 8SOctanoateOctanoate (N-C8:0)Octanoic acidOctanoic acid (N-C8:0)OctoateOctoic acidOctylateOctylic acidPrifac 2901C8H16O2144.2114144.115029756octanoic acidcaprylic acid124-07-2CCCCCCCC(O)=OInChI=1S/C8H16O2/c1-2-3-4-5-6-7-8(9)10/h2-7H2,1H3,(H,9,10)WWZKQHOCKIZLMA-UHFFFAOYSA-NLiquidMembranelogp2.92logs-2.20solubility9.07e-01 g/lmelting_point16.5 oClogp2.7pka_strongest_acidic5.19iupacoctanoic acidaverage_mass144.2114mono_mass144.115029756smilesCCCCCCCC(O)=OformulaC8H16O2inchiInChI=1S/C8H16O2/c1-2-3-4-5-6-7-8(9)10/h2-7H2,1H3,(H,9,10)inchikeyWWZKQHOCKIZLMA-UHFFFAOYSA-Npolar_surface_area37.3refractivity40.28polarizability17.4rotatable_bond_count6acceptor_count2donor_count1physiological_charge-1formal_charge0Fatty acid biosynthesisThe fatty acid biosynthesis starts from acetyl-CoA reacting either with a holo-[acp] through a 3-oxoacyl-[acp] synthase 3 resulting in an acetyl-[acp] or react with hydrogen carbonate through an ATP driven acetyl-CoA carboxylase resulting in a malonyl-CoA.
Malonyl-CoA reacts with a holo-acp] through a malonyl-CoA-ACP transacylase resulting in a malonyl-[acp]. This compound can react with a KASI protein resulting in an acetyl-[acp]. A malonyl-[acp] can also react with an acetyl-[acp] through KASI and KASII or with acetyl-CoA through a beta-ketoacyl-ACP synthase to produce an acetoacetyl-[acp]. An acetoacetyl-[acp] is also known as a 3-oxoacyl-[acp].
A 3-oxoacyl-[acp] is reduced through a NDPH mediated 3-oxoacyl-[acp] reductase resulting in a (3R)-3-hydroxyacyl-[acp] (R3 hydroxydecanoyl-[acp]) which can either join the fatty acid metabolism, be dehydrated by an 3R-hydroxymyristoyl-[acp] dehydratase to produce a trans-2-enoyl-[acp] or be dehydrated by a hydroxydecanoyl-[acp] to produce a trans-delta2 decenoyl-[acp].
Trans-2-enoyl-[acp] is reduced by a NADH driven enoyl-[acp] reductase resulting in a 2,3,4-saturated fatty acyl-[acp]. This product then reacts with malonyl-[acp] through KASI and KASII resulting in a holo-acyl carrier protein and a 3- oxoacyl-[acp].
Trans-delta2 decenoyl-[acp] reacts with a 3-hydroxydecanoyl-[acp] dehydrase producing a cis-delta 3-decenoyl-ACP. This product then reacts with KASI to produce a 3-oxo-cis-delta5-dodecenoyl-[acp], which in turn is reduced by a NADPH driven 3-oxoacyl-[acp] resulting in a 3R-hydroxy cis delta5-dodecenoyl-acp. This product is dehydrated by a (3R)-hydroxymyristoyl-[acp] dehydratase resulting in a trans-delta 3- cis-delta 5-dodecenoyl-[acp] which in turn is reduced by a NADH driven enoyl-[acp] reductase resulting in a cis-delta5-dodecenoyl-acp which goes into fatty acid metabolism
PW000900ec00061MetabolicLipoic acid metabolismLipoic 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 .
PW000770ec00785Metabolicfatty acid oxidation (octanoate)Although enzymes of the pathway handle both short and long chain fatty acids, it is the long chain compounds that induce the enzymes of the pathway . Each turn of the cycle removes two carbon atoms until only two or three remain. When even-numbered fatty acids are broken down, a two-carbon compound remains, acetyl-CoA. When odd number fatty acids are broken down, a three-carbon residue results, propionylCoA. Unsaturated fatty acids, with cis double bonds located at odd-numbered carbon atoms, enter the main pathway of saturated fatty acid degradation by converting related metabolites of cis configuration and D stereoisomers, derived from breakdown of unsaturated fatty acids, to the trans- or L isomers of saturated fatty acid breakdown by an isomerase and an epimerase, respectively. When cis double bonds are located at even-numbered carbon atoms, such as linoleic acid (cis,cis(9,12)-octadecadienoic acid), after the fatty acid is degraded to the ten carbon stage an extra step is required to deal with the resulting compound, trans,δ(2)-cis,δ(4)decadienoyl-CoA. The enzyme 2,4-dienoyl-CoA reductase, converts this to trans,δ(2)decenoyl-CoA which enters the normal cycle at the point of the isomerase.
The order of the reaction is as follows:
a 2,3,4 saturated fatty acid is transformed into a 2,3,4 saturated fatty acyl CoA through a Long and short chain fatty acid CoA ligase. The 2,3,4 saturated fatty acyl CoA is then transformed into a trans 2 enoyl CoA. This enoyl can also be produced from a cis 3 enoyl CoA through a fatty acid oxidation protein complex. The trans 2 enoyl is transformed into a 3s 3 hydroxyacyl CoA through a 2,3 dehydroadipyl CoA hydratase. This same enzyme turns the product into a 3-oxoacyl-CoA. This is followed by the last step in the reaction when the oxoacyl-coa is turn into an acetyl coa+ a 2,3,4 saturated fatty acyl CoA through a 3-ketoacyl-CoA thiolasePW001022Metaboliclipoate biosynthesis and incorporation IIPWY0-1275Specdb::CMs557Specdb::CMs991Specdb::CMs2501Specdb::CMs29469Specdb::CMs30118Specdb::CMs30644Specdb::CMs31152Specdb::CMs31993Specdb::CMs37560Specdb::CMs162715Specdb::CMs1063271Specdb::EiMs896Specdb::NmrOneD1389Specdb::NmrOneD2206Specdb::NmrOneD2900Specdb::NmrOneD4932Specdb::NmrOneD4933Specdb::MsMs698Specdb::MsMs699Specdb::MsMs700Specdb::MsMs4096Specdb::MsMs4097Specdb::MsMs4098Specdb::MsMs178293Specdb::MsMs178294Specdb::MsMs178295Specdb::MsMs180609Specdb::MsMs180610Specdb::MsMs180611Specdb::MsMs374162Specdb::MsMs437424Specdb::MsMs437425Specdb::MsMs438695Specdb::MsMs2244259Specdb::MsMs2245853Specdb::MsMs2246424Specdb::MsMs2697189Specdb::MsMs2697190Specdb::MsMs2697191Specdb::MsMs2981813Specdb::MsMs2981814Specdb::MsMs2981815Specdb::NmrTwoD1333HMDB00482370C0642328837CPD-195OCACaprylic acidKeseler, I. M., Collado-Vides, J., Santos-Zavaleta, A., Peralta-Gil, M., Gama-Castro, S., Muniz-Rascado, L., Bonavides-Martinez, C., Paley, S., Krummenacker, M., Altman, T., Kaipa, P., Spaulding, A., Pacheco, J., Latendresse, M., Fulcher, C., Sarker, M., Shearer, A. G., Mackie, A., Paulsen, I., Gunsalus, R. P., Karp, P. D. (2011). "EcoCyc: a comprehensive database of Escherichia coli biology." Nucleic Acids Res 39:D583-D590.21097882Kanehisa, M., Goto, S., Sato, Y., Furumichi, M., Tanabe, M. (2012). "KEGG for integration and interpretation of large-scale molecular data sets." Nucleic Acids Res 40:D109-D114.22080510Winder, C. L., Dunn, W. B., Schuler, S., Broadhurst, D., Jarvis, R., Stephens, G. M., Goodacre, R. (2008). "Global metabolic profiling of Escherichia coli cultures: an evaluation of methods for quenching and extraction of intracellular metabolites." Anal Chem 80:2939-2948.18331064Yurtsever D. (2007). Fatty acid methyl ester profiling of Enterococcus and Esherichia coli for microbial source tracking. M.sc. Thesis. Villanova University: U.S.AHoffmann GF, Meier-Augenstein W, Stockler S, Surtees R, Rating D, Nyhan WL: Physiology and pathophysiology of organic acids in cerebrospinal fluid. J Inherit Metab Dis. 1993;16(4):648-69.8412012Giannakou SA, Dallas PP, Rekkas DM, Choulis NH: In vitro evaluation of nimodipine permeation through human epidermis using response surface methodology. Int J Pharm. 2002 Jul 8;241(1):27-34.12086718Dieterle F, Muller-Hagedorn S, Liebich HM, Gauglitz G: Urinary nucleosides as potential tumor markers evaluated by learning vector quantization. Artif Intell Med. 2003 Jul;28(3):265-79.12927336Nair MK, Joy J, Venkitanarayanan KS: Inactivation of Enterobacter sakazakii in reconstituted infant formula by monocaprylin. J Food Prot. 2004 Dec;67(12):2815-9.15633694Habeeb AF, Francis RD: Preparation of human immunoglobulin by caprylic acid precipitation. Prep Biochem. 1984;14(1):1-17.6718324Caprylic acid. Jpn. Kokai Tokkyo Koho (1983), 4 pp. http://hmdb.ca/system/metabolites/msds/000/000/401/original/HMDB00482.pdf?1358463203Acyl carrier protein phosphodiesteraseP21515ACPH_ECOLIacpHhttp://ecmdb.ca/proteins/P21515.xmlBifunctional protein aasP31119AAS_ECOLIaashttp://ecmdb.ca/proteins/P31119.xmlLipoate-protein ligase AP32099LPLA_ECOLIlplAhttp://ecmdb.ca/proteins/P32099.xmlLong-chain-fatty-acid--CoA ligaseP69451LCFA_ECOLIfadDhttp://ecmdb.ca/proteins/P69451.xmlShort-chain-fatty-acid--CoA ligaseP38135FADK_ECOLIfadKhttp://ecmdb.ca/proteins/P38135.xmlAcyl-CoA thioesterase 2P0AGG2TESB_ECOLItesBhttp://ecmdb.ca/proteins/P0AGG2.xmlAcyl carrier proteinP0A6A8ACP_ECOLIacpPhttp://ecmdb.ca/proteins/P0A6A8.xmlOuter membrane protein NP77747OMPN_ECOLIompNhttp://ecmdb.ca/proteins/P77747.xmlOuter membrane pore protein EP02932PHOE_ECOLIphoEhttp://ecmdb.ca/proteins/P02932.xmlOuter membrane protein FP02931OMPF_ECOLIompFhttp://ecmdb.ca/proteins/P02931.xmlOuter membrane protein CP06996OMPC_ECOLIompChttp://ecmdb.ca/proteins/P06996.xmlAdenosine triphosphate + Coenzyme A + Hydrogen ion + Caprylic acid > Adenosine monophosphate + Hydrogen ion + Octanoyl-CoA + Pyrophosphateacyl carrier protein + Adenosine triphosphate + Caprylic acid > Adenosine monophosphate + Octanoyl-ACP (n-C8:0ACP) + PyrophosphateWater + Octanoyl-ACP (n-C8:0ACP) > acyl carrier protein + Hydrogen ion + Caprylic acidWater + Octanoyl-CoA > Coenzyme A + Hydrogen ion + Caprylic acidAdenosine triphosphate + Hydrogen ion + Caprylic acid > Adenosine monophosphate + octanoate (protein bound) + PyrophosphateCaprylic acid + Adenosine triphosphate + a [lipoyl-carrier protein]-L-lysine > Hydrogen ion + Pyrophosphate + Adenosine monophosphate + Protein N6-(octanoyl)lysinePW_R003563Caprylic acid + Adenosine triphosphate + Coenzyme A > Adenosine monophosphate + Octanoyl-CoA + Octanoyl-CoAPW_R003763Caprylic acid + a holo-[acyl-carrier protein] + Adenosine triphosphate > Octanoyl-[acyl-carrier protein] + Adenosine monophosphate + PyrophosphatePW_R003562