Disease relevance of crotonyl-S-CoA

• During the subsequent dehydration of D-3-hydroxybutyryl-CoA the pro-2S hydrogen and the 3-hydroxyl group are removed in a syn elimination to form crotonyl-CoA [1].
• ccr encoding crotonyl coenzyme A (CoA) reductase (CCR), which catalyzes the conversion of crotonyl-CoA to butyryl-CoA in the presence of NADPH, was previously cloned from Streptomyces collinus [2].
• The decarboxylation of glutaconyl-CoA to crotonyl-CoA in the anaerobic bacterium Acidaminococcus fermentans is catalysed by a membrane-bound, biotin-dependent enzyme which requires Na+ for activity [3].
• The crotonyl-CoA reductase gene was cloned in Escherichia coli [4].
• Steady-state kinetics, equilibrium binding, and primary substrate kinetic isotope effect studies revealed that the reduction of crotonyl-CoA by NADH, catalyzed by Haemophilus influenzae enoyl-ACP reductase (FabI), follows a rapid equilibrium random kinetic mechanism with negative interaction among the substrates [5].

High impact information on crotonyl-S-CoA

• Glutaryl-CoA dehydrogenase catalyzes the oxidation and decarboxylation of glutaryl-CoA to crotonyl-CoA and CO(2) [6].
• It showed NADH-dependent enoyl-acyl carrier protein (ACP) reductase activity using both crotonyl-ACP and crotonyl-CoA as substrates [7].
• Glutaryl-CoA dehydrogenase, a multifunctional enzyme responsible for dehydrogenation and decarboxylation of glutaryl-CoA to crotonyl-CoA, has been purified 1,680-fold from porcine liver mitochondria [8].
• These bands corresponded to pyruvate carboxylase (Mr = 125,000), the biotin-containing subunit of methyl crotonyl-CoA carboxylase (Mr = 75,000) and the biotin-containing subunit of propionyl-CoA carboxylase (Mr = 73,000) as judged by molecular weight markers, purified carboxylase protein standards, and interaction with monospecific antisera [9].
• All enzymes except for 3-ketoacyl-CoA thiolase were protected against this inactivation by either NADH or crotonyl-CoA [10].

Chemical compound and disease context of crotonyl-S-CoA

• Role of crotonyl coenzyme A reductase in determining the ratio of polyketides monensin A and monensin B produced by Streptomyces cinnamonensis [11].
• A crotonyl-CoA reductase (EC 1.3.1.38, acyl-CoA:NADP+ trans-2-oxidoreductase) catalyzing the conversion of crotonyl-CoA to butyryl-CoA has been purified and characterized from Streptomyces collinus [4].
• The ccr gene product was expressed in E. coli and the induced crotonyl-CoA reductase was purified tenfold and shown to have similar steady-state kinetics and electrophoretic mobility on sodium dodecyl sulfate/polyacrylamide to the native protein [4].
• Decarboxylation of glutamate leads to 4-aminobutyrate, which is fermented by a second organism via the fourth pathway to acetate and butyrate, again mediated by an unusual dehydratase which catalyses the reversible dehydration of 4-hydroxybutyryl-CoA to crotonyl-CoA [12].
• Recombinant Ralstonia eutropha capable of producing poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) copolymer [P(3HB-co-3HHx)] from fructose was engineered by introduction of genes for crotonyl-CoA reductase (CCR) from Streptomyces cinnamonensis (ccrSc) and for PHA synthase and (R)-specific enoyl-CoA hydratase from Aeromonas caviae (phaC-JAc) [13].

Biological context of crotonyl-S-CoA

• Oxidation-reduction of general acyl-CoA dehydrogenase by the butyryl-CoA/crotonyl-CoA couple. A new investigation of the rapid reaction kinetics [14].
• The ccr gene, encoding crotonyl coenzyme A (CoA) reductase (CCR), was cloned from Streptomyces cinnamonensis C730.1 and shown to encode a protein with 90% amino acid sequence identity to the CCRs of Streptomyces collinus and Streptomyces coelicolor [11].
• The redox dye-linked oxidation of crotonyl-CoA (with inhibited respiratory chain) was also higher in gently disrupted mitochondria (149%) than in disrupted ones [15].

Anatomical context of crotonyl-S-CoA

• Disruption of echA led to a 28-fold reduction in 2-butenoyl-CoA hydratase activity in a preparation of organelles [16].
• Three species of enoyl-CoA reductase, distinct from each other by their chain-length specificity, were found in Euglena mitochondria, and one of them was highly specific for crotonyl-CoA [17].
• Stereospecificity as well as the dependency on reduced pyridine nucleotides of the enzymatic reduction of acetoacetyl CoA and crotonyl CoA in lactating rabbit mammary glands are reported [18].
• Studies of the specificity of the 5 alpha-reductase activity in human prostate microsomes have shown that conversion of testosterone into DHT (Km = 12 nmol/l) was competitively inhibited by crotonyl CoA (Ki = 125 mumol/l), a model substrate for enoyl CoA reductase of the microsomal fatty acid elongase system [19].

Associations of crotonyl-S-CoA with other chemical compounds

• Catalysis of the syn hydration of crotonyl-CoA, absent in the wild-type 4-chlorobenzoyl-CoA dehalogenase, was shown to occur with the structurally modified 4-chlorobenzoyl-CoA dehalogenase at kcat = 0.06 s-1 and Km = 50 microM [20].
• The dehydratase catalyses the reversible conversion of 4-hydroxybutyryl-CoA (Km = 50 microM) to crotonyl-CoA and possesses a probably intrinsic vinylacetyl-CoA delta 3-delta 2-isomerase with a specific activity of 223 nkat mg-1 [21].
• The respiration-linked oxidation of crotonyl-CoA and 3-hydroxybutyryl-CoA proceeded at much higher rates (over 700%) in gently disrupted mitochondria than in completely disrupted mitochondria [15].

Gene context of crotonyl-S-CoA

• Enzymatic analysis of tagged MaoC showed that MaoC has enoyl-CoA hydratase activity toward crotonyl-CoA [22].
• Crotonyl-CoA complexation, however, shifted the reduction potential of the Glu367Gln SCAD mutant protein by 30 mV in the positive direction [23].
• A second 29-kDa enoyl-CoA hydratase acted on crotonyl-CoA; this highly active enoyl-CoA hydratase also acted slowly on cyclohex-1-ene-1-carbonyl-CoA [24].
• In this recombinant strain, C6-acyl-CoA intermediates were provided via beta-ketothiolase-mediated elongation of butyryl-CoA, which was generated from crotonyl-CoA by the function of CCR [13].

References