| Definition | (4z,7z)-9-[(1s,2r,3r)-3-hydroxy-2-[(1e,3s,5z)-3-hydroxyocta-1,5-dien-1-yl]-5-oxocyclopentyl]nona-4,7-dienoyl-coa is an acyl-CoA or acyl-coenzyme A. More specifically, it is a (4Z_7Z)-9-[(1S_2R_3R)-3-hydroxy-2-[(1E_3S_5Z)-3-hydroxyocta-1_5-dien-1-yl]-5-oxocyclopentyl]nona-4_7-dienoic acid thioester of coenzyme A. (4z,7z)-9-[(1s,2r,3r)-3-hydroxy-2-[(1e,3s,5z)-3-hydroxyocta-1,5-dien-1-yl]-5-oxocyclopentyl]nona-4,7-dienoyl-coa is an acyl-CoA with 22 fatty acid group as the acyl moiety attached to coenzyme A. Coenzyme A was discovered in 1946 by Fritz Lipmann (Journal of Biological Chemistry (1946) 162 (3): 743–744) and its structure was determined in the early 1950s at the Lister Institute in London. Coenzyme A is a complex, thiol-containing molecule that is naturally synthesized from pantothenate (vitamin B5), which is found in various foods such as meat, vegetables, cereal grains, legumes, eggs, and milk. More specifically, coenzyme A (CoASH or CoA) consists of a beta-mercaptoethylamine group linked to the vitamin pantothenic acid (B5) through an amide linkage and 3'-phosphorylated ADP. Coenzyme A is synthesized in a five-step process that requires four molecules of ATP, pantothenate and cysteine. It is believed that there are more than 1100 types of acyl-CoA’s in the human body, which also corresponds to the number of acylcarnitines in the human body. Acyl-CoAs exists in all living species, ranging from bacteria to plants to humans. The general role of acyl-CoA’s is to assist in transferring fatty acids from the cytoplasm to mitochondria. This process facilitates the production of fatty acids in cells, which are essential in cell membrane structure. Acyl-CoA's are also susceptible to beta oxidation, forming, ultimately, acetyl-CoA. Acetyl-CoA can enter the citric acid cycle, eventually forming several equivalents of ATP. In this way, fats are converted to ATP -- or biochemical energy. Acyl-CoAs can be classified into 9 different categories depending on the size of their acyl-group: 1) short-chain acyl-CoAs; 2) medium-chain acyl-CoAs; 3) long-chain acyl-CoAs; and 4) very long-chain acyl-CoAs; 5) hydroxy acyl-CoAs; 6) branched chain acyl-CoAs; 7) unsaturated acyl-CoAs; 8) dicarboxylic acyl-CoAs and 9) miscellaneous acyl-CoAs. Short-chain acyl-CoAs have acyl-groups with two to four carbons (C2-C4), medium-chain acyl-CoAs have acyl-groups with five to eleven carbons (C5-C11), long-chain acyl-CoAs have acyl-groups with twelve to twenty carbons (C12-C20) while very long-chain acyl-CoAs have acyl groups with more than 20 carbons. (4z,7z)-9-[(1s,2r,3r)-3-hydroxy-2-[(1e,3s,5z)-3-hydroxyocta-1,5-dien-1-yl]-5-oxocyclopentyl]nona-4,7-dienoyl-coa is therefore classified as a very long chain acyl-CoA. The oxidative degradation of fatty acids is a two-step process, catalyzed by acyl-CoA synthetase/synthase. Fatty acids are first converted to their acyl phosphate, the precursor to acyl-CoA. The latter conversion is mediated by acyl-CoA synthase. Three types of acyl-CoA synthases are employed, depending on the chain length of the fatty acid. (4z,7z)-9-[(1s,2r,3r)-3-hydroxy-2-[(1e,3s,5z)-3-hydroxyocta-1,5-dien-1-yl]-5-oxocyclopentyl]nona-4,7-dienoyl-coa, being a very long chain acyl-CoA is a substrate for very long chain acyl-CoA synthase. The second step of fatty acid degradation is beta oxidation. Beta oxidation occurs in mitochondria and, in the case of very long chain acyl-CoAs, the peroxisome. After its formation in the cytosol, (4Z,7Z)-9-[(1S,2R,3R)-3-hydroxy-2-[(1E,3S,5Z)-3-hydroxyocta-1,5-dien-1-yl]-5-oxocyclopentyl]nona-4,7-dienoyl-CoA is transported into the mitochondria, the locus of beta oxidation. Transport of (4Z,7Z)-9-[(1S,2R,3R)-3-hydroxy-2-[(1E,3S,5Z)-3-hydroxyocta-1,5-dien-1-yl]-5-oxocyclopentyl]nona-4,7-dienoyl-CoA into the mitochondria requires carnitine palmitoyltransferase 1 (CPT1), which converts (4Z,7Z)-9-[(1S,2R,3R)-3-hydroxy-2-[(1E,3S,5Z)-3-hydroxyocta-1,5-dien-1-yl]-5-oxocyclopentyl]nona-4,7-dienoyl-CoA into (4Z_7Z)-9-[(1S_2R_3R)-3-hydroxy-2-[(1E_3S_5Z)-3-hydroxyocta-1_5-dien-1-yl]-5-oxocyclopentyl]nona-4_7-dienoylcarnitine, which gets transported into the mitochondrial matrix. Once in the matrix, (4Z_7Z)-9-[(1S_2R_3R)-3-hydroxy-2-[(1E_3S_5Z)-3-hydroxyocta-1_5-dien-1-yl]-5-oxocyclopentyl]nona-4_7-dienoylcarnitine is converted back to (4Z,7Z)-9-[(1S,2R,3R)-3-hydroxy-2-[(1E,3S,5Z)-3-hydroxyocta-1,5-dien-1-yl]-5-oxocyclopentyl]nona-4,7-dienoyl-CoA by CPT2, whereupon beta-oxidation can begin. Beta oxidation of (4Z,7Z)-9-[(1S,2R,3R)-3-hydroxy-2-[(1E,3S,5Z)-3-hydroxyocta-1,5-dien-1-yl]-5-oxocyclopentyl]nona-4,7-dienoyl-CoA occurs in four steps. First, since (4Z,7Z)-9-[(1S,2R,3R)-3-hydroxy-2-[(1E,3S,5Z)-3-hydroxyocta-1,5-dien-1-yl]-5-oxocyclopentyl]nona-4,7-dienoyl-CoA is a very long chain acyl-CoA it is the substrate for a very long chain acyl-CoA dehydrogenase, which catalyzes dehydrogenation of (4Z,7Z)-9-[(1S,2R,3R)-3-hydroxy-2-[(1E,3S,5Z)-3-hydroxyocta-1,5-dien-1-yl]-5-oxocyclopentyl]nona-4,7-dienoyl-CoA, creating a double bond between the alpha and beta carbons. FAD is the hydrogen acceptor, yielding FADH2. Second, Enoyl-CoA hydrase catalyzes the addition of water across the newly formed double bond to make an alcohol. Third, 3-hydroxyacyl-CoA dehydrogenase oxidizes the alcohol group to a ketone and NADH is produced from NAD+. Finally, Thiolase cleaves between the alpha carbon and ketone to release one molecule of acetyl-CoA and a new acyl-CoA which is now 2 carbons shorter. This four-step process repeats until (4Z,7Z)-9-[(1S,2R,3R)-3-hydroxy-2-[(1E,3S,5Z)-3-hydroxyocta-1,5-dien-1-yl]-5-oxocyclopentyl]nona-4,7-dienoyl-CoA has had all its carbons removed from the chain, leaving only acetyl-CoA. Beta oxidation, as well as alpha-oxidation, also occurs in the peroxisome. The peroxisome handles beta oxidation of fatty acids that have more than 20 carbons in their chain because the peroxisome contains very-long-chain Acyl-CoA synthetases and dehydrogenases. The heart primarily metabolizes fat for energy and Acyl-CoA metabolism has been identified as a critical molecule in early-stage heart muscle pump failure. Cellular acyl-CoA content also correlates with insulin resistance, suggesting that it can mediate lipotoxicity in non-adipose tissues. Acyl-CoA: diacylglycerol acyltransferase (DGAT) plays an important role in energy metabolism on account of key enzyme in triglyceride biosynthesis. The study of acyl-CoAs is an active area of research and it is likely that many novel acyl-CoAs will be discovered in the coming years. It is also likely that many novel roles in health and disease will be uncovered for these molecules. |
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| Structure | CCC=CCC(O)C=CC1C(O)CC(=O)C1CC=CCC=CCCC(=O)SCCNC(=O)CCNC(=O)C(O)C(C)(C)COP(O)(=O)OP(O)(=O)OCC1OC(C(O)C1OP(O)(O)=O)N1C=NC2=C1N=CN=C2N InChI=1S/C43H66N7O20P3S/c1-4-5-10-13-27(51)16-17-29-28(30(52)22-31(29)53)14-11-8-6-7-9-12-15-34(55)74-21-20-45-33(54)18-19-46-41(58)38(57)43(2,3)24-67-73(64,65)70-72(62,63)66-23-32-37(69-71(59,60)61)36(56)42(68-32)50-26-49-35-39(44)47-25-48-40(35)50/h5,7-11,16-17,25-29,31-32,36-38,42,51,53,56-57H,4,6,12-15,18-24H2,1-3H3,(H,45,54)(H,46,58)(H,62,63)(H,64,65)(H2,44,47,48)(H2,59,60,61) |
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| InChI Identifier | InChI=1S/C43H66N7O20P3S/c1-4-5-10-13-27(51)16-17-29-28(30(52)22-31(29)53)14-11-8-6-7-9-12-15-34(55)74-21-20-45-33(54)18-19-46-41(58)38(57)43(2,3)24-67-73(64,65)70-72(62,63)66-23-32-37(69-71(59,60)61)36(56)42(68-32)50-26-49-35-39(44)47-25-48-40(35)50/h5,7-11,16-17,25-29,31-32,36-38,42,51,53,56-57H,4,6,12-15,18-24H2,1-3H3,(H,45,54)(H,46,58)(H,62,63)(H,64,65)(H2,44,47,48)(H2,59,60,61) |
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