| Definition | (5z,8z,10e,14z,17z)-12-hydroxyicosa-5,8,10,14,17-pentaenoyl-coa is an acyl-CoA or acyl-coenzyme A. More specifically, it is a (5Z_8Z_10E_14Z_17Z)-12-hydroxyicosa-5_8_10_14_17-pentaenoic acid thioester of coenzyme A. (5z,8z,10e,14z,17z)-12-hydroxyicosa-5,8,10,14,17-pentaenoyl-coa is an acyl-CoA with 20 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. (5z,8z,10e,14z,17z)-12-hydroxyicosa-5,8,10,14,17-pentaenoyl-coa is therefore classified as a 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. (5z,8z,10e,14z,17z)-12-hydroxyicosa-5,8,10,14,17-pentaenoyl-coa, being a long chain acyl-CoA is a substrate for 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, (5Z,8Z,10E,14Z,17Z)-12-hydroxyicosa-5,8,10,14,17-pentaenoyl-CoA is transported into the mitochondria, the locus of beta oxidation. Transport of (5Z,8Z,10E,14Z,17Z)-12-hydroxyicosa-5,8,10,14,17-pentaenoyl-CoA into the mitochondria requires carnitine palmitoyltransferase 1 (CPT1), which converts (5Z,8Z,10E,14Z,17Z)-12-hydroxyicosa-5,8,10,14,17-pentaenoyl-CoA into (5Z_8Z_10E_14Z_17Z)-12-hydroxyicosa-5_8_10_14_17-pentaenoylcarnitine, which gets transported into the mitochondrial matrix. Once in the matrix, (5Z_8Z_10E_14Z_17Z)-12-hydroxyicosa-5_8_10_14_17-pentaenoylcarnitine is converted back to (5Z,8Z,10E,14Z,17Z)-12-hydroxyicosa-5,8,10,14,17-pentaenoyl-CoA by CPT2, whereupon beta-oxidation can begin. Beta oxidation of (5Z,8Z,10E,14Z,17Z)-12-hydroxyicosa-5,8,10,14,17-pentaenoyl-CoA occurs in four steps. First, since (5Z,8Z,10E,14Z,17Z)-12-hydroxyicosa-5,8,10,14,17-pentaenoyl-CoA is a long chain acyl-CoA it is the substrate for a long chain acyl-CoA dehydrogenase, which catalyzes dehydrogenation of (5Z,8Z,10E,14Z,17Z)-12-hydroxyicosa-5,8,10,14,17-pentaenoyl-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 (5Z,8Z,10E,14Z,17Z)-12-hydroxyicosa-5,8,10,14,17-pentaenoyl-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=CCC(O)C=CC=CCC=CCCCC(=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/C41H64N7O18P3S/c1-4-5-6-7-12-15-18-29(49)19-16-13-10-8-9-11-14-17-20-32(51)70-24-23-43-31(50)21-22-44-39(54)36(53)41(2,3)26-63-69(60,61)66-68(58,59)62-25-30-35(65-67(55,56)57)34(52)40(64-30)48-28-47-33-37(42)45-27-46-38(33)48/h5-6,9-13,15-16,19,27-30,34-36,40,49,52-53H,4,7-8,14,17-18,20-26H2,1-3H3,(H,43,50)(H,44,54)(H,58,59)(H,60,61)(H2,42,45,46)(H2,55,56,57) |
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| InChI Identifier | InChI=1S/C41H64N7O18P3S/c1-4-5-6-7-12-15-18-29(49)19-16-13-10-8-9-11-14-17-20-32(51)70-24-23-43-31(50)21-22-44-39(54)36(53)41(2,3)26-63-69(60,61)66-68(58,59)62-25-30-35(65-67(55,56)57)34(52)40(64-30)48-28-47-33-37(42)45-27-46-38(33)48/h5-6,9-13,15-16,19,27-30,34-36,40,49,52-53H,4,7-8,14,17-18,20-26H2,1-3H3,(H,43,50)(H,44,54)(H,58,59)(H,60,61)(H2,42,45,46)(H2,55,56,57) |
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