2,4 Dienoyl-CoA reductase

Unlike the breakdown of saturated fat, cis and trans polyunsaturated fatty acid degradation requires three additional enzymes to generate a product compatible with the standard beta oxidation pathway.Substrate length for mDECR catalysis is thought to be limited at 20 carbons, at which this very long chain fatty acid is first partially oxidized by pDECR in the peroxisome.In the final step, a proton is abstracted from the water[11] to the Cα and the thioester is reformed, resulting in a single Cβ-Cγ trans double bond.[8] 2,4 Dienoyl-CoA Reductase from Escherichia coli shares very similar kinetic properties to that of eukaryotes, but differs significantly in both structure and mechanism.[11] The active site contains accurately positioned Tyr166 that donates a proton to the Cγ after hydride attack at the Cδ, completing the reduction in a single concerted step.[8] The structure of the ternary complex of pDCR (peroxisomal 2,4-dienoyl CoA reductases) with NADP and its substrate provides essential and unique insights into the mechanism of catalysis.
Crystallization [ 7 ] of DECR with 2,4 Hexadienoyl-CoA and NADPH (not shown). Key residues in the enzyme active site orient the substrate for hydride transfer through a network of hydrogen bonds.
Proposed mechanism of 2,4-Trans dienoyl-CoA reduction by NADPH in mammalian DECR. The mechanism proceeds stepwise through an enolate intermediate.
RefSeqUniProtEC numberChr. 8enzymechromosome 8beta oxidationenoyl CoA isomerasestereoselectivestereospecificmitochondriaperoxisomehomologouspost-translational modificationRossmann foldhomotetrameramino acidsEscherichia coliiron–sulfur clusterunsaturated fattyternary complexcatalysistyrosineserineaspartatelysineprotonshort chain fatty acidsmitochondrionperoxisomesvery long chain fatty acids2,4 Dienoyl-CoA reductase deficiencyknockout miceoleic acidpalmitoleic acidlinoleic acidlinolenic aciddiurnalstressors2,4-dienoyl-CoA reductase 1Medical Subject HeadingsMetabolismlipid metabolismfatty acid metabolismtriglyceridefatty acidenzymesMalonyl-CoAATP citrate lyaseAcetyl-CoA carboxylaseFatty acid synthesisFatty acid synthaseBeta-ketoacyl-ACP synthaseΒ-Ketoacyl ACP reductase3-Hydroxyacyl ACP dehydraseEnoyl ACP reductasedesaturasesStearoyl-CoA desaturase-1Glycerol-3-phosphate dehydrogenaseThiokinaseDegradationCarnitine palmitoyltransferase ICarnitine-acylcarnitine translocaseCarnitine palmitoyltransferase IIAcyl CoA dehydrogenaseACADVLACADSBEnoyl-CoA hydrataseAcetyl-CoA C-acyltransferasePropionyl-CoA carboxylaseHydroxyacyl-Coenzyme A dehydrogenaseacetyl-CoAMalonyl-CoA decarboxylaseAldehydesLong-chain-aldehyde dehydrogenaseOxidoreductasesCH–CH oxidoreductasesEnoyl-acyl carrier protein reductase7-Dehydrocholesterol reductaseBiliverdin reductaseDihydroxymethyloxo-tetrahydroquinoline dehydrogenaseOxygenDihydroorotate dehydrogenaseCoproporphyrinogen III oxidaseProtoporphyrinogen oxidaseBilirubin oxidaseAcyl-CoA oxidaseDihydrouracil oxidaseTetrahydroberberine oxidaseSecologanin synthaseTryptophan alpha,beta-oxidasePyrroloquinoline-quinone synthaseL-galactonolactone oxidaseQuinoneSuccinate dehydrogenaseFumarate reductaseButyryl-CoA dehydrogenase5α-reductaseSRD5A1SRD5A2SRD5A3Glutaryl-CoA dehydrogenaseIsovaleryl coenzyme A dehydrogenase3-oxo-5beta-steroid 4-dehydrogenaseActive siteBinding siteCatalytic triadOxyanion holeEnzyme promiscuityDiffusion-limited enzymeCofactorEnzyme catalysisAllosteric regulationCooperativityEnzyme inhibitorEnzyme activatorEnzyme superfamilyEnzyme familyList of enzymesEnzyme kineticsEadie–Hofstee diagramHanes–Woolf plotLineweaver–Burk plotMichaelis–Menten kineticsTransferasesHydrolasesLyasesIsomerasesLigasesTranslocases