branched-chain fatty acyl-CoA |
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CHEBI:61912 |
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A fatty acyl-CoA that results from the formal condensation of the thiol group of coenzyme A with the carboxy group of any branched-chain fatty acid. |
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This entity has been manually annotated by the ChEBI Team.
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acyl donor
Any donor that can transfer acyl groups between molecular entities.
(via acyl-CoA )
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View more via ChEBI Ontology
branched-chain FA-CoA
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ChEBI
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branched-chain FA-coenzyme A
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ChEBI
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branched-chain fatty acyl-CoAs
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ChEBI
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branched-chain fatty acyl-coenzyme A
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ChEBI
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branched-chain fatty acyl-coenzyme As
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ChEBI
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Hostetler HA, Kier AB, Schroeder F (2006) Very-long-chain and branched-chain fatty acyl-CoAs are high affinity ligands for the peroxisome proliferator-activated receptor alpha (PPARalpha). Biochemistry 45, 7669-7681 [PubMed:16768463] [show Abstract] Very-long-chain fatty acids (VLCFA) and branched-chain fatty acids (BCFA) are potent inducers of the peroxisome proliferator-activated receptor PPARalpha, a nuclear receptor that enhances transcription of peroxisomal enzymes mediating beta-oxidation of these potentially toxic fatty acids. However, it is not known whether the respective free fatty acids or their activated metabolites, i.e., CoA thioesters, (i) are the endogenous high-affinity PPARalpha ligands, (ii) alter PPARalpha conformation, and (iii) alter recruitment of coregulatory proteins to PPARalpha. As shown by quenching of PPARalpha intrinsic amino acid fluorescence, PPARalpha exhibited high affinity (3-29 nM Kds) for the CoA thioesters of the common (C20-C24) VLCFA. In contrast, with the exception of arachidonic acid (Kd = 20 nM), PPARalpha only weakly bound the VLCFA. PPARalpha also exhibited higher affinity for the CoA thioesters of BCFA (phytanoyl-CoA, pristanoyl-CoA; Kds near 11 nM) than for the respective free branched-chain fatty acids. As shown by circular dichroism, the high affinity VLCFA-CoA and BCFA-CoA strongly altered PPARalpha conformation. Likewise, the high affinity VLCFA-CoA and BCFA-CoA altered cofactor recruitment to PPARalpha as shown by coimmunoprecipitation from liver homogenates. In contrast, nearly all the respective free fatty acids elicited only weak conformational changes in PPARalpha and did not alter cofactor recruitment to PPARalpha. In summary, the CoA thioesters of very-long-chain and branched-chain fatty acids are much more potent PPARalpha ligands than the free acids, resulting in altered PPARalpha conformation and cofactor recruitment. Since these are hallmarks of ligand-activated nuclear receptors, this suggests that the CoA thioesters are the active forms of these PPARalpha ligands. | Seedorf U, Raabe M, Ellinghaus P, Kannenberg F, Fobker M, Engel T, Denis S, Wouters F, Wirtz KW, Wanders RJ, Maeda N, Assmann G (1998) Defective peroxisomal catabolism of branched fatty acyl coenzyme A in mice lacking the sterol carrier protein-2/sterol carrier protein-x gene function. Genes & development 12, 1189-1201 [PubMed:9553048] [show Abstract] Gene targeting in mice was used to investigate the unknown function of Scp2, encoding sterol carrier protein-2 (SCP2; a peroxisomal lipid carrier) and sterol carrier protein-x (SCPx; a fusion protein between SCP2 and a peroxisomal thiolase). Complete deficiency of SCP2 and SCPx was associated with marked alterations in gene expression, peroxisome proliferation, hypolipidemia, impaired body weight control, and neuropathy. Along with these abnormalities, catabolism of methyl-branched fatty acyl CoAs was impaired. The defect became evident from up to 10-fold accumulation of the tetramethyl-branched fatty acid phytanic acid in Scp2(-/-) mice. Further characterization supported that the gene disruption led to inefficient import of phytanoyl-CoA into peroxisomes and to defective thiolytic cleavage of 3-ketopristanoyl-CoA. These results corresponded to high-affinity binding of phytanoyl-CoA to the recombinant rat SCP2 protein, as well as high 3-ketopristanoyl-CoA thiolase activity of the recombinant rat SCPx protein. | Van Veldhoven PP, Vanhove G, Vanhoutte F, Dacremont G, Parmentier G, Eyssen HJ, Mannaerts GP (1991) Identification and purification of a peroxisomal branched chain fatty acyl-CoA oxidase. The Journal of biological chemistry 266, 24676-24683 [PubMed:1761563] [show Abstract] Isoprenoid (branched) fatty acids such as pristanic acid can be degraded via beta-oxidation in peroxisomes. We synthesized 2-methylpalmitoyl-CoA as a model substrate in order to study the first step of the peroxisomal beta-oxidation of branched fatty acids, catalyzed by an acyl-CoA oxidase. 2-Methylpalmitoyl-CoA oxidase activity was found in rat liver homogenates. Subcellular fractionation demonstrated that the oxidase was confined to peroxisomes. 2-Methylpalmitoyl-CoA oxidase was also present in kidney and intestine. It was not induced in liver or in the extrahepatic tissues by treatment of rats with peroxisome proliferators or by feeding diets containing excess isoprenoids. The enzyme was partially purified together with palmitoyl-CoA oxidase and trihydroxycoprostanoyl-CoA oxidase by heat treatment and ammonium sulfate fractionation of liver extracts. The partially purified preparation was chromatographed on various columns. 2-Methylpalmitoyl-CoA oxidase could be separated from the inducible (by peroxisome proliferators) palmitoyl-CoA oxidase and from trihydroxycoprostanoyl-CoA oxidase, but it always coeluted with the noninducible palmitoyl-CoA oxidase, recently described by us (Schepers, L., Van Veldhoven, P. P., Casteels, M., Eyssen, H. J., and Mannaerts, G. P. (1990) J. Biol. Chem. 265, 5242-5246). 2-Methylpalmitoyl-CoA oxidase was purified to near homogeneity in three chromatographic steps (anion exchange, hydroxylapatite, and gel filtration). Its apparent molecular mass is approximately 415 kDa, and it consists of identical subunits of approximately 70 kDa. The enzyme oxidized 2-methylpalmitoyl-CoA twice as rapidly as palmitoyl-CoA and pristanoyl-CoA as rapidly as palmitoyl-CoA, so that it can be considered as a branched fatty acyl-CoA oxidase. Since pristanoyl-CoA is one of its naturally occurring substrates we propose to name this enzyme pristanoyl-CoA oxidase. |
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