Enzymes
UniProtKB help_outline | 4,984 proteins |
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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 hexadecanoyl-CoA Identifier CHEBI:57379 Charge -4 Formula C37H62N7O17P3S InChIKeyhelp_outline MNBKLUUYKPBKDU-BBECNAHFSA-J SMILEShelp_outline [C@@H]1(N2C3=C(C(=NC=N3)N)N=C2)O[C@H](COP(OP(OCC(C)([C@H](C(NCCC(NCCSC(CCCCCCCCCCCCCCC)=O)=O)=O)O)C)(=O)[O-])(=O)[O-])[C@H]([C@H]1O)OP([O-])([O-])=O 2D coordinates Mol file for the small molecule Search links Involved in 110 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)-hexadecenoyl-CoA Identifier CHEBI:61526 Charge -4 Formula C37H60N7O17P3S InChIKeyhelp_outline JUPAQFRKPHPXLD-MSHHSVQMSA-J SMILEShelp_outline [C@@H]1(N2C3=C(C(=NC=N3)N)N=C2)O[C@H](COP(OP(OCC([C@H](C(NCCC(NCCSC(=O)/C=C/CCCCCCCCCCCCC)=O)=O)O)(C)C)(=O)[O-])(=O)[O-])[C@H]([C@H]1O)OP([O-])([O-])=O 2D coordinates Mol file for the small molecule Search links Involved in 10 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:43448 | RHEA:43449 | RHEA:43450 | RHEA:43451 | |
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Reaction direction help_outline | undefined | left-to-right | right-to-left | bidirectional |
UniProtKB help_outline |
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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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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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Targeted disruption of mouse long-chain acyl-CoA dehydrogenase gene reveals crucial roles for fatty acid oxidation.
Kurtz D.M., Rinaldo P., Rhead W.J., Tian L., Millington D.S., Vockley J., Hamm D.A., Brix A.E., Lindsey J.R., Pinkert C.A., O'Brien W.E., Wood P.A.
Abnormalities of fatty acid metabolism are recognized to play a significant role in human disease, but the mechanisms remain poorly understood. Long-chain acyl-CoA dehydrogenase (LCAD) catalyzes the initial step in mitochondrial fatty acid oxidation (FAO). We produced a mouse model of LCAD deficie ... >> More
Abnormalities of fatty acid metabolism are recognized to play a significant role in human disease, but the mechanisms remain poorly understood. Long-chain acyl-CoA dehydrogenase (LCAD) catalyzes the initial step in mitochondrial fatty acid oxidation (FAO). We produced a mouse model of LCAD deficiency with severely impaired FAO. Matings between LCAD +/-mice yielded an abnormally low number of LCAD +/- and -/-offspring, indicating frequent gestational loss. LCAD -/-mice that reached birth appeared normal, but had severely reduced fasting tolerance with hepatic and cardiac lipidosis, hypoglycemia, elevated serum free fatty acids, and nonketotic dicarboxylic aciduria. Approximately 10% of adult LCAD -/-males developed cardiomyopathy, and sudden death was observed in 4 of 75 LCAD -/-mice. These results demonstrate the crucial roles of mitochondrial FAO and LCAD in vivo. << Less
Proc. Natl. Acad. Sci. U.S.A. 95:15592-15597(1998) [PubMed] [EuropePMC]
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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.