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evolution
based on the chain length of the substrates, the HAD family is divided into three subclasses: 3-hydroxyacyl-CoA dehydrogenases (HADs), long-chain 3-hydroxyacyl-CoA dehydrogenases (LCHADs) and short-chain 3-hydroxyacyl-CoA dehydrogenases (SCHADs). HADs are soluble dimeric enzymes that exhibit substrate specificity for an acyl-chain length of C4-C10 and are previously referred to as short-chain HADs
evolution
Caenorhabditis elegans HAD is highly conserved to human HAD
evolution
Caenorhabditis elegans HAD is highly conserved to human HAD
evolution
two (S)-3-hydroxyacyl-CoA dehydrogenase/enoyl-CoA hydratases, H16_A0461/FadB' and H16_A1526/FadB1, are involved in the FA degradation in Ralstonia eutropha H16. FadB' and FadB1 possess an enoyl-CoA hydratase activity, catalyzing hydrogenation of the unsaturated enoyl coenzyme A (CoA), and a 3-hydroxyacyl-CoA dehydrogenase activity, i.e. oxidation of the hydroxyl group into a keto group using one NAD+ molecule
evolution
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two (S)-3-hydroxyacyl-CoA dehydrogenase/enoyl-CoA hydratases, H16_A0461/FadB' and H16_A1526/FadB1, are involved in the FA degradation in Ralstonia eutropha H16. FadB' and FadB1 possess an enoyl-CoA hydratase activity, catalyzing hydrogenation of the unsaturated enoyl coenzyme A (CoA), and a 3-hydroxyacyl-CoA dehydrogenase activity, i.e. oxidation of the hydroxyl group into a keto group using one NAD+ molecule
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malfunction
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mice lacking SCHAD, hadh-/-, display a lower body weight and a reduced fat mass in comparison with hadh+/+ mice under high-fat diet conditions, presumably due to an impaired fuel efficiency, the loss of acylcarnitines via the urine, and increased body temperature. Food intake, total energy expenditure, and locomotor activity are not altered in knockout mice
malfunction
a null mutant of fadB2 shows no significant differences from the wild-type strain with regard to lipid composition, utilization of different fatty acid carbon sources and tolerance to various stresses
malfunction
mutantions with attenuated interactions on the dimerization interface significantly decrease the enzyme activity compared to the wild-type. Such reduced activities are in consistency with the reduced ratios of the catalytic intermediate formation. Further molecular dynamics simulations results reveal that the alteration of the dimerization interface will increase the fluctuation of a distal region that plays an important role in the substrate binding. The increased fluctuation decreases the stability of the catalytic intermediate formation, and therefore the enzymatic activity is attenuated
malfunction
mutations in HADH cause hyperinsulinemic hypoglycemia that is precipitated by protein in a similar manner to the hyperinsulinism/hyperammonemia (HI/HA) syndrome, which is caused by mutations in the GLUD1 gene, encoding the enzyme glutamate dehydrogenase (GDH), suggesting a link between mitochondrial fatty acid oxidation, amino acid metabolism, and insulin secretion, clinical phenotypes, overview
malfunction
numerous human diseases are found related to mutations at HAD dimerization interface that is away from the catalytic pocket
malfunction
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a null mutant of fadB2 shows no significant differences from the wild-type strain with regard to lipid composition, utilization of different fatty acid carbon sources and tolerance to various stresses
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metabolism
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the enzyme catalyzes the third reaction of the mitochondrial beta-oxidation cascade, the oxidation of 3-hydroxyacyl-CoA to 3-ketoacyl-CoA, for medium-andshort-chain fatty acids
metabolism
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the enzyme is the penultimate enzyme of mitochondrial fatty acid beta-oxidation
metabolism
the enzyme is involved in benzoyl-coenzyme A degradation
metabolism
the enzyme is involved in beta-oxidation cycle
metabolism
3-hydroxyacyl-CoA dehydrogenase catalyzes the third step in fatty acid beta-oxidation
metabolism
3-hydroxyacyl-CoA dehydrogenase catalyzes the third step in fatty acid beta-oxidation
metabolism
3-hydroxyacyl-CoA dehydrogenase catalyzes the third step in fatty acid beta-oxidation, oxidizing the hydroxyl group of 3-hydroxyacyl-CoA to a keto group
metabolism
the enzyme catalyzes the second step in the biosynthesis of n-butanol from acetyl-CoA by the reduction of acetoacetyl-CoA to 3-hydroxybutyryl-CoA
metabolism
the enzyme catalyzes the second step in the biosynthesis of n-butanol from acetyl-CoA by the reduction of acetoacetyl-CoA to 3-hydroxybutyryl-CoA
metabolism
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the enzyme catalyzes the second step in the biosynthesis of n-butanol from acetyl-CoA by the reduction of acetoacetyl-CoA to 3-hydroxybutyryl-CoA
metabolism
the enzyme is involved in fatty acid degradation metabolism
metabolism
the enzyme specifically catalyzes the third step of beta oxidation
metabolism
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the enzyme is involved in benzoyl-coenzyme A degradation
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metabolism
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the enzyme is involved in beta-oxidation cycle
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metabolism
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the enzyme is involved in fatty acid degradation metabolism
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metabolism
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the enzyme specifically catalyzes the third step of beta oxidation
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metabolism
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the enzyme catalyzes the second step in the biosynthesis of n-butanol from acetyl-CoA by the reduction of acetoacetyl-CoA to 3-hydroxybutyryl-CoA
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physiological function
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PaaH functions as an NAD+-dependent [probably (S)-3specific] 3-hydroxyadipyl-CoA dehydrogenase forming 3-oxoadipyl-CoA in the aerobic phenylacetate pathway, overview
physiological function
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PaaH functions as an NAD+-dependent [probably (S)-3specific] 3-hydroxyadipyl-CoA dehydrogenase forming 3-oxoadipyl-CoA in the aerobic phenylacetate pathway, overview
physiological function
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the enzyme is involved in thermogenesis, in the maintenance of body weight, and in the regulation of nutrient-stimulated insulin secretion. It plays an important role in adaptive thermogenesis
physiological function
the enzyme is involved in autotrophic carbon fixation
physiological function
the enzyme is involved in the 3-hydroxypropionate/4-hydroxybutyrate carbon fixation pathway
physiological function
important role for HADH in insulin secretion
physiological function
the enzyme is classified as an oxidoreductase in fatty acid metabolic processes. It specifically catalyzes the third step of beta oxidation. Long-chain fatty acids are utilized by Leptospira as the sole carbon source and are metabolized by beta-oxidation. Therefore, a large amount of HADH may be produced intracellularly and released to get carbons and energy by oxidizing free fatty acid
physiological function
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PaaH functions as an NAD+-dependent [probably (S)-3specific] 3-hydroxyadipyl-CoA dehydrogenase forming 3-oxoadipyl-CoA in the aerobic phenylacetate pathway, overview
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physiological function
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the enzyme is involved in the 3-hydroxypropionate/4-hydroxybutyrate carbon fixation pathway
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physiological function
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the enzyme is involved in autotrophic carbon fixation
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physiological function
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the enzyme is classified as an oxidoreductase in fatty acid metabolic processes. It specifically catalyzes the third step of beta oxidation. Long-chain fatty acids are utilized by Leptospira as the sole carbon source and are metabolized by beta-oxidation. Therefore, a large amount of HADH may be produced intracellularly and released to get carbons and energy by oxidizing free fatty acid
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additional information
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enzyme-protein interaction analysis in different tissues and subcellular compartments, detailed overview
additional information
conserved catalytic residues are Ser119, His140, and Asn190
additional information
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conserved catalytic residues are Ser119, His140, and Asn190
additional information
FadB' is an enzyme with two catalytic domains exhibiting a single monomeric structure and possessing a molecular weight of 86 kDa. The C-terminal part of the enzyme harbors enoyl-CoA hydratase activity, EC 4.2.1.17, and is able to convert trans-crotonyl-CoA to 3-hydroxybutyryl-CoA. The N-terminal part of FadB' comprises an NAD+ binding site and is responsible for 3-hydroxyacyl-CoA dehydrogenase activity converting (S)-3-hydroxybutyryl-CoA to acetoacetyl-CoA
additional information
molecular mechanism about the essential role of the HAD dimerization interface in its catalytic activity via allosteric effects, molecular dynamics simulation, overview
additional information
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molecular mechanism about the essential role of the HAD dimerization interface in its catalytic activity via allosteric effects, molecular dynamics simulation, overview
additional information
molecular mechanism about the essential role of the HAD dimerization interface in its catalytic activity via allosteric effects, molecular dynamics simulation, overview
additional information
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molecular mechanism about the essential role of the HAD dimerization interface in its catalytic activity via allosteric effects, molecular dynamics simulation, overview
additional information
the adenosine diphosphate moiety of NAD+ is not highly stabilized compared with the remainder of the acetoacetyl-CoA molecule
additional information
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the adenosine diphosphate moiety of NAD+ is not highly stabilized compared with the remainder of the acetoacetyl-CoA molecule
additional information
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FadB' is an enzyme with two catalytic domains exhibiting a single monomeric structure and possessing a molecular weight of 86 kDa. The C-terminal part of the enzyme harbors enoyl-CoA hydratase activity, EC 4.2.1.17, and is able to convert trans-crotonyl-CoA to 3-hydroxybutyryl-CoA. The N-terminal part of FadB' comprises an NAD+ binding site and is responsible for 3-hydroxyacyl-CoA dehydrogenase activity converting (S)-3-hydroxybutyryl-CoA to acetoacetyl-CoA
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additional information
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conserved catalytic residues are Ser119, His140, and Asn190
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