This enzyme, characterized from eukaryotic organisms, catalyses the reduction of either (2E,4E)-2,4-dienoyl-CoA or (2E,4Z)-2,4-dienoyl-CoA to (3E)-3-enoyl-CoA. The best substrates for the enzyme from bovine liver have a chain-length of 8 or 10 carbons. Mammals possess both mitochondrial and peroxisomal variants of this enzyme. cf. EC 1.3.1.34, 2,4-dienoyl-CoA reductase [(2E)-enoyl-CoA-producing].
a (2E)-2-enoyl-CoA + NADP+ = a (2E,4E)-2,4-dienoyl-CoA + NADPH + H+
reaction mechanism, enzyme-ligand interactions in a distinctive short-chain reductase active site, catalytic site structure, stabilization of the dienolate reaction intermediate by Tyr199 and Asn148, and NADP+, overview
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SYSTEMATIC NAME
IUBMB Comments
(3E)-3-enoyl-CoA:NADP+ 4-oxidoreductase
This enzyme, characterized from eukaryotic organisms, catalyses the reduction of either (2E,4E)-2,4-dienoyl-CoA or (2E,4Z)-2,4-dienoyl-CoA to (3E)-3-enoyl-CoA. The best substrates for the enzyme from bovine liver have a chain-length of 8 or 10 carbons. Mammals possess both mitochondrial and peroxisomal variants of this enzyme. cf. EC 1.3.1.34, 2,4-dienoyl-CoA reductase [(2E)-enoyl-CoA-producing].
enzyme is the key enzyme of beta-oxidation of unsaturated fatty acid in mitochondria and to a lesser extent in peroxisomes, three accessory proteins are involved in the pathway
DECR may also play a role in the degradation of fatty acids containing odd-numbered double bonds because the intermediate 2,5-dienoyl-CoA may be isomerized by enoyl-CoA isomerase to 3,5-dienoyl-CoA and then converted to 2,4-dienoyl-CoA by a specific delta3,5,delta2,4-dienoyl-CoA isomerase
in eukaryotes, double bonds in even-numbered positions are reduced by an NADPH-dependent 2,4-dienoyl-CoA reductase to 3-enoyl-CoA, which is then isomerized by enoyl-CoA isomerase to trans-2-enoyl-CoA, suitable for further oxidation
enzyme is the key enzyme of beta-oxidation of unsaturated fatty acid in mitochondria and to a lesser extent in peroxisomes, three accessory proteins are involved in the pathway
DECR may also play a role in the degradation of fatty acids containing odd-numbered double bonds because the intermediate 2,5-dienoyl-CoA may be isomerized by enoyl-CoA isomerase to 3,5-dienoyl-CoA and then converted to 2,4-dienoyl-CoA by a specific delta3,5,delta2,4-dienoyl-CoA isomerase
in eukaryotes, double bonds in even-numbered positions are reduced by an NADPH-dependent 2,4-dienoyl-CoA reductase to 3-enoyl-CoA, which is then isomerized by enoyl-CoA isomerase to trans-2-enoyl-CoA, suitable for further oxidation
reductase activity for wild-type and Decr-/- mice, the observed residual activity represents the activity of mitochondrial 2-enoyl thioester reductase, which functions in mitochondrial fatty acid synthesis and can also reduce 2,4-hexadienoyl-CoA in vitro
analysis of liver fatty acids after the mice are fasted for 24 h indicates that fasting has a minor effect on the lipid content of wild type liver, with an overall increase of 29% in the concentration of fatty acids, in Decr-/- mice, the overall concentration of fatty acids increases by 108% after fasting
fasting increases the total concentration of acylcarnitines by 2fold in wild type mice (567 nM), in Decr-/- mice, a markedly higher 9fold increase is observed (2150 nM)
immunoblotting of mitochondrial extracts from liver, muscle and heart with an antibody against human DECR reveals a detectable signal from wild type mice, whereas no signal can be detected for homozygous null mutant mice
in Decr-/- mice, the overall concentration of fatty acids increases by 108% after fasting, the most profound changes between fasted wild type and Decr-/- mice are observed for the levels of palmitoleic acid (C16:1), oleic acid, linolenic acid (C18:3) and linoleic acid, which are 2.5- to 3.8fold higher in Decr-/- mice, in comparison to the fed state, the concentrations of monounsaturated fatty acids and polyunsaturated fatty acids increase by 288% and 254%, respectively
mitochondrial 2,4-dienoyl-CoA reductase activity in mice is indispensable for the complete oxidation of (poly)unsaturated fatty acids and for adaptation to metabolic stress
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CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
wild-type and selenomethionine enzyme, 0.001 ml of protein and of reservoir solution, the latter containing 16% PEG 4000 w/v, 0.18 M ammonium sulfate, 80 mM sodium acetate, pH 4.6, 20% glycerol, addition of 30% ethylene glycol and 4 mM NADP+ for the binary complex of enzyme with NADP+, and 120 mM substrate for the ternary complex of enzyme with NADP+ and substrate trans-trans-2,4-dienoyl-CoA, X-ray diffraction structure determination and analysis at 2.1 A and 1.75 A resolution, respectively
site-directed mutagenesis, mutant is expressed in inclusion bodies and cannot be refolded to a functional enzyme after extraction from inclusion bodies with 8 M urea as denatured protein
synthesis of polyhydroxyalkanoate from 10-trans-heptadecenoic acid in mutants devoid of 2,4-dienoyl-CoA reductase reveals degradation of the trans fatty acid directly via the enoyl-CoA hydratase II activity of the multifunctional enzyme. Level of polyhydroxyalkanoate is 10-25% to that of wild-type in mutants lacking 2,4-dienoyl-CoA reductase
synthesis of polyhydroxyalkanoate from 10-trans-heptadecenoic acid in mutants devoid of 2,4-dienoyl-CoA reductase reveals degradation of the trans fatty acid directly via the enoyl-CoA hydratase II activity of the multifunctional enzyme. Level of polyhydroxyalkanoate is 10-25% to that of wild-type in mutants lacking 2,4-dienoyl-CoA reductase
recombinant His-tagged truncated wild-type and of mutant enzymes from Escherichia coli strain BL21(DE3) by one-step nickel affinity chromatography, to over 95% purity
creation of a DECR-deficient mouse line, fasted Decr-/- mice display increased serum acylcarnitines, especially decadienoylcarnitine, a product of the incomplete oxidation of linoleic acid (C18:2), urinary excretion of unsaturated dicarboxylic acids, and hepatic steatosis, wherein unsaturated fatty acids accumulate in liver triacylglycerols, metabolically challenged Decr-/- mice turn on ketogenesis, but unexpectedly develop hypoglycemia
overexpression of His-tagged truncated wild-type and of mutant enzymes in Escherichia coli strain BL21(DE3), expression as soluble protein, except for mutant D117A
overexpression of His-tagged wild-type and mutant enzymes in Escherichia coli strain BL21(DE3), expression of selenomethionine enzyme in Escherichia coli strain B834(DE3)
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RENATURED/Commentary
ORGANISM
UNIPROT
LITERATURE
mutant D117A is expressed in inclusion bodies and cannot be refolded to a functional enzyme after extraction from inclusion bodies with 8 M urea as denatured protein
A role for 2,4-enoyl-CoA reductase in mitochondrial beta-oxidation of polyunsaturated fatty acids. Effects of treatment with clofibrate on oxidation of polyunsaturated acylcarnitines by isolated rat liver mitochondria
Degradation of unsaturated fatty acids. Identification of intermediates in the degradation of cis-4-decenoyl-CoA by extracts of beef-liver mitochondria
Borrebaek, B.; Osmundsen, H.; Christiansen, E.N.; Bremer, J.
Increased 4-enoyl-CoA reductase activity in liver mitochondria of rats fed high-fed diets and its effect on fatty acid oxidation and the inhibitory action of pent-4-enoate
Structure and reactivity of human mitochondrial 2,4-dienoyl-CoA reductase: enzyme-ligand interactions in a distinctive short-chain reductase active site
Robert, J.; Marchesini, S.; Delessert, S.; Poirier, Y.
Analysis of the beta-oxidation of trans-unsaturated fatty acid in recombinant Saccharomyces cerevisiae expressing a peroxisomal PHA synthase reveals the involvement of a reductase-dependent pathway
Effects of pectin pentaoligosaccharide from Hawthorn (Crataegus pinnatifida Bunge. var. Major) on the activity and mRNA levels of enzymes involved in fatty acid oxidation in the liver of mice fed a high-fat diet