Reaction participants Show >> << Hide
- Name help_outline octadecanoyl-CoA Identifier CHEBI:57394 Charge -4 Formula C39H66N7O17P3S InChIKeyhelp_outline SIARJEKBADXQJG-LFZQUHGESA-J SMILEShelp_outline CCCCCCCCCCCCCCCCCC(=O)SCCNC(=O)CCNC(=O)[C@H](O)C(C)(C)COP([O-])(=O)OP([O-])(=O)OC[C@H]1O[C@H]([C@H](O)[C@@H]1OP([O-])([O-])=O)n1cnc2c(N)ncnc12 2D coordinates Mol file for the small molecule Search links Involved in 62 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
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Namehelp_outline
oxidized [electron-transfer flavoprotein]
Identifier
RHEA-COMP:10685
Reactive part
help_outline
- Name help_outline FAD Identifier CHEBI:57692 Charge -3 Formula C27H30N9O15P2 InChIKeyhelp_outline IMGVNJNCCGXBHD-UYBVJOGSSA-K SMILEShelp_outline Cc1cc2nc3c(nc(=O)[n-]c3=O)n(C[C@H](O)[C@H](O)[C@H](O)COP([O-])(=O)OP([O-])(=O)OC[C@H]3O[C@H]([C@H](O)[C@@H]3O)n3cnc4c(N)ncnc34)c2cc1C 2D coordinates Mol file for the small molecule Search links Involved in 172 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline H+ Identifier CHEBI:15378 Charge 1 Formula H InChIKeyhelp_outline GPRLSGONYQIRFK-UHFFFAOYSA-N SMILEShelp_outline [H+] 2D coordinates Mol file for the small molecule Search links Involved in 9,521 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline (2E)-octadecenoyl-CoA Identifier CHEBI:71412 Charge -4 Formula C39H64N7O17P3S InChIKeyhelp_outline NBCCUIHOHUKBMK-ZDDAFBBHSA-J SMILEShelp_outline CCCCCCCCCCCCCCC\C=C\C(=O)SCCNC(=O)CCNC(=O)[C@H](O)C(C)(C)COP([O-])(=O)OP([O-])(=O)OC[C@H]1O[C@H]([C@H](O)[C@@H]1OP([O-])([O-])=O)n1cnc2c(N)ncnc12 2D coordinates Mol file for the small molecule Search links Involved in 7 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
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Namehelp_outline
reduced [electron-transfer flavoprotein]
Identifier
RHEA-COMP:10686
Reactive part
help_outline
- Name help_outline FADH2 Identifier CHEBI:58307 Charge -2 Formula C27H33N9O15P2 InChIKeyhelp_outline YPZRHBJKEMOYQH-UYBVJOGSSA-L SMILEShelp_outline Cc1cc2Nc3c([nH]c(=O)[nH]c3=O)N(C[C@H](O)[C@H](O)[C@H](O)COP([O-])(=O)OP([O-])(=O)OC[C@H]3O[C@H]([C@H](O)[C@@H]3O)n3cnc4c(N)ncnc34)c2cc1C 2D coordinates Mol file for the small molecule Search links Involved in 163 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Cross-references
RHEA:47240 | RHEA:47241 | RHEA:47242 | RHEA:47243 | |
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Reaction direction help_outline | undefined | left-to-right | right-to-left | bidirectional |
UniProtKB help_outline |
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MetaCyc help_outline |
Related reactions help_outline
More general form(s) of this reaction
Publications
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Relationship between structure and substrate-chain-length specificity of mitochondrial very-long-chain acyl-coenzyme A dehydrogenase.
Souri M., Aoyama T., Yamaguchi S., Hashimoto T.
Very-long-chain acyl-coenzyme A dehydrogenase (VLCAD) is one of four enzymes which catalyze the initial step of the mitochondrial beta-oxidation with different but overlapping substrate-chain-length specificities. A450P, a variant of VLCAD identified in a patient with VLCAD deficiency, showed abno ... >> More
Very-long-chain acyl-coenzyme A dehydrogenase (VLCAD) is one of four enzymes which catalyze the initial step of the mitochondrial beta-oxidation with different but overlapping substrate-chain-length specificities. A450P, a variant of VLCAD identified in a patient with VLCAD deficiency, showed abnormal substrate-chain-length specificity. Based on this mutation, we studied the relationship between the structure and substrate-chain-length specificity of VLCAD. When VLCAD was treated with trypsin, a homodimer protein of a 48-kDa polypeptide deprived of both the amino-terminal 22 amino acids and the carboxyl-terminal 145 amino acids of VLCAD was obtained. Six Ala450 variants and tryptic-VLCAD exhibited similar substrate specificities. Effects of long-chain acyl-CoA on the tryptic cleavage and changes in the catalytic properties by deprivation of the carboxyl-terminal region suggest that this region interacts with the fatty acyl moiety of long-chain acyl-CoA. Thus, both Ala450 and the carboxyl-terminal region, which are not shared by other acyl-CoA dehydrogenases, are likely to be the determinating factors in the substrate-chain-length specificity of VLCAD. << Less
Eur. J. Biochem. 257:592-598(1998) [PubMed] [EuropePMC]
This publication is cited by 2 other entries.
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Human acyl-CoA dehydrogenase-9 plays a novel role in the mitochondrial beta-oxidation of unsaturated fatty acids.
Ensenauer R., He M., Willard J.M., Goetzman E.S., Corydon T.J., Vandahl B.B., Mohsen A.W., Isaya G., Vockley J.
Unsaturated fatty acids play an important role in the prevention of human diseases such as diabetes, obesity, cancer, and neurodegeneration. However, their oxidation in vivo by acyl-CoA dehydrogenases (ACADs) that catalyze the first step of each cycle of mitochondrial fatty acid beta-oxidation is ... >> More
Unsaturated fatty acids play an important role in the prevention of human diseases such as diabetes, obesity, cancer, and neurodegeneration. However, their oxidation in vivo by acyl-CoA dehydrogenases (ACADs) that catalyze the first step of each cycle of mitochondrial fatty acid beta-oxidation is not entirely understood. Recently, a novel ACAD (ACAD-9) of unknown function that is highly homologous to human very-long-chain acyl-CoA dehydrogenase was identified by large-scale random sequencing. To characterize its enzymatic role, we have expressed ACAD-9 in Escherichia coli, purified it, and determined its pattern of substrate utilization. The N terminus of the mature form of the enzyme was identified by in vitro mitochondrial import studies of precursor protein. A 37-amino acid leader peptide was cleaved sequentially by two mitochondrial peptidases to yield a predicted molecular mass of 65 kDa for the mature subunit. Submitochondrial fractionation studies found native ACAD-9 to be associated with the mitochondrial membrane. Gel filtration analysis indicated that, like very-long-chain acyl-CoA dehydrogenase, ACAD-9 is a dimer, in contrast to the other known ACADs, which are tetramers. Purified mature ACAD-9 had maximal activity with long-chain unsaturated acyl-CoAs as substrates (C16:1-, C18:1-, C18:2-, C22:6-CoA). These results suggest a previously unrecognized role for ACAD-9 in the mitochondrial beta-oxidation of long-chain unsaturated fatty acids. Because of the substrate specificity and abundance of ACAD-9 in brain, we speculate that it may play a role in the turnover of lipid membrane unsaturated fatty acids that are essential for membrane integrity and structure. << Less
J. Biol. Chem. 280:32309-32316(2005) [PubMed] [EuropePMC]
This publication is cited by 20 other entries.
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Expression and characterization of mutations in human very long-chain acyl-CoA dehydrogenase using a prokaryotic system.
Goetzman E.S., Wang Y., He M., Mohsen A.W., Ninness B.K., Vockley J.
Very long-chain acyl-CoA dehydrogenase (VLCAD) catalyzes the first enzymatic step in the mitochondrial beta-oxidation of fatty acids 14-20 carbons in length. More than 100 cases of VLCAD deficiency have been reported with the disease varying from a severe, often fatal neonatal form to a mild adult ... >> More
Very long-chain acyl-CoA dehydrogenase (VLCAD) catalyzes the first enzymatic step in the mitochondrial beta-oxidation of fatty acids 14-20 carbons in length. More than 100 cases of VLCAD deficiency have been reported with the disease varying from a severe, often fatal neonatal form to a mild adult-onset form. VLCAD is distinguished from matrix-soluble acyl-CoA dehydrogenases by its unique C-terminal domain, homodimeric structure, and localization to the inner mitochondrial membrane. We have for the first time expressed and purified VLCAD using a bacterial system. Recombinant VLCAD had similar biochemical properties to those reported for native VLCAD and the bacterial system was used to study six previously described disease-causing missense mutations including the two most common mild mutations (T220M, V243A), a mutation leading to the severe disease phenotype (R429W), and three mutations in the C-terminal domain (A450P, L462P, and R573W). Of particular interest was the finding that the A450P and L462P bacterial extracts had normal or increased amounts of VLCAD antigen and activity. In the pure form L462P had roughly 30% of wild-type activity while A450P was normal. Using computer modeling both mutations were mapped to a predicted charged surface of VLCAD that we postulate interacts with the mitochondrial membrane. In a membrane pull down assay both mutants showed greatly reduced mitochondrial membrane association, suggesting a mechanism for the disease in these patients. In summary, the bacterial expression system developed here will significantly advance our understanding of both the clinical aspects of VLCAD deficiency and the basic biochemistry of the enzyme. << Less
Mol. Genet. Metab. 91:138-147(2007) [PubMed] [EuropePMC]
This publication is cited by 5 other entries.
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Medium-long-chain chimeric human Acyl-CoA dehydrogenase: medium-chain enzyme with the active center base arrangement of long-chain Acyl-CoA dehydrogenase.
Nandy A., Kieweg V., Kraeutle F.G., Vock P., Kuechler B., Bross P., Kim J.J., Rasched I., Ghisla S.
The catalytically essential glutamate residue that initiates catalysis by abstracting the substrate alpha-hydrogen as H+ is located at position 376 (mature MCADH numbering) on loop JK in medium chain acyl-CoA dehydrogenase (MCADH). In long chain acyl-CoA dehydrogenase (LCADH) and isovaleryl-CoA de ... >> More
The catalytically essential glutamate residue that initiates catalysis by abstracting the substrate alpha-hydrogen as H+ is located at position 376 (mature MCADH numbering) on loop JK in medium chain acyl-CoA dehydrogenase (MCADH). In long chain acyl-CoA dehydrogenase (LCADH) and isovaleryl-CoA dehydrogenase (IVDH), the corresponding Glu carrying out the same function is placed at position 255 on the adjacent helix G. These glutamates thus act on substrate approaching from two opposite regions at the active center. We have implemented the topology of LCADH in MCADH by carrying out the two mutations Glu376Gly and Thr255Glu. The resulting chimeric enzyme, "medium-/long" chain acyl-CoA dehydrogenase (MLCADH) has approximately 20% of the activity of MCADH and approximately 25% that of LCADH with its best substrates octanoyl-CoA and dodecanoyl-CoA, respectively. MLCADH exhibits an enhanced rate of reoxidation with oxygen, however, with a much narrower substrate chain length specificity that peaks with dodecanoyl-CoA. This is the same maximum as that of LCADH and is thus significantly shifted from that of native MCADH (hexanoyl/octanoyl-CoA). The putative, common ancestor of LCADH and IVDH has two Glu residues, one each at positions 255 and 376. The corresponding MCADH mutant, Thr255Glu (glu/glu-MCADH), is as active as MCADH with octanoyl-CoA; its activity/chain length profile is, however, much narrower. The topology of the Glu as H+ abstracting base seems an important factor in determining chain length specificity and reactivity in acyl-CoA dehydrogenases. The mechanisms underlying these effects are discussed in view of the three-dimensional structure of MLCADH, which is presented in the accompanying paper [Lee et al. (1996) Biochemistry 35, 12412-12420]. << Less
Biochemistry 35:12402-12411(1996) [PubMed] [EuropePMC]
This publication is cited by 6 other entries.
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Identification and characterization of new long chain acyl-CoA dehydrogenases.
He M., Pei Z., Mohsen A.W., Watkins P., Murdoch G., Van Veldhoven P.P., Ensenauer R., Vockley J.
Long-chain fatty acids are an important source of energy in muscle and heart where the acyl-CoA dehydrogenases (ACADs) participate in consecutive cycles of β-oxidation to generate acetyl-CoA and reducing equivalents for generating energy. However, the role of long-chain fatty acid oxidation in the ... >> More
Long-chain fatty acids are an important source of energy in muscle and heart where the acyl-CoA dehydrogenases (ACADs) participate in consecutive cycles of β-oxidation to generate acetyl-CoA and reducing equivalents for generating energy. However, the role of long-chain fatty acid oxidation in the brain and other tissues that do not rely on fat for energy is poorly understood. Here we characterize two new ACADs, ACAD10 and ACAD11, both with significant expression in human brain. ACAD11 utilizes substrates with primary carbon chain lengths between 20 and 26, with optimal activity towards C22CoA. The combination of ACAD11 with the newly characterized ACAD9 accommodates the full spectrum of long chain fatty acid substrates presented to mitochondrial β-oxidation in human cerebellum. ACAD10 has significant activity towards the branched-chain substrates R and S, 2 methyl-C15-CoA and is highly expressed in fetal but not adult brain. This pattern of expression is similar to that of LCAD, another ACAD previously shown to be involved in long branched chain fatty acid metabolism. Interestingly, the ACADs in human cerebellum were found to have restricted cellular distribution. ACAD9 was most highly expressed in the granular layer, ACAD11 in the white matter, and MCAD in the molecular layer and axons of specific neurons. This compartmentalization of ACADs in the human central nerve system suggests that β-oxidation in cerebellum participates in different functions other than generating energy, for example, the synthesis and/or degradation of unique cellular lipids and catabolism of aromatic amino acids, compounds that are vital to neuronal function. << Less
Mol. Genet. Metab. 102:418-429(2011) [PubMed] [EuropePMC]
This publication is cited by 13 other entries.