Disease relevance of butyryl-CoA

• The acsA gene product expressed in Escherichia coli showed acyl-CoA synthetase activity toward butyric acid and CoA as substrates, with butyryl-CoA being synthesized [1].
• No significant increase in activity of the enzymes butyryl-CoA synthetase, crotonase or hydroxybutyryl-CoA dehydrogenase was found in patients with ulcerative colitis [2].
• The final steps in butyrate synthesis by anaerobic bacteria can occur via butyrate kinase and phosphotransbutyrylase or via butyryl-coenzyme A (CoA):acetate CoA-transferase [3].
• Butyryl-CoA synthetase of Pseudomonas aeruginosa--purification and characterization [4].
• An acyl-coenzyme A carboxylase that carboxylates acetyl-CoA, butyryl-CoA, propionyl-CoA, and succinyl-CoA was purified from Myxococcus xanthus [5].

High impact information on butyryl-CoA

• A soluble extract of rat liver mitochondria catalyzed the isomerization of 2-trans-5-cis-octadienoyl-CoA to 2-trans-4-trans-octadienoyl-CoA, which upon addition of NADPH, NAD+, and CoA was chain-shortened to hexanoyl-CoA, butyryl-CoA, and acetyl-CoA [6].
• In contrast, mitochondrial butyryl-CoA dehydrogenase [butyryl-CoA: (acceptor) oxidoreductase, EC 1.3.99.2] activity in these cells was preserved at normal levels [7].
• Hence, the possible involvement of the rat hepatic microsomal short chain beta-ketoacyl-CoA reductase, short chain beta-hydroxyacyl-CoA dehydratase, and the previously reported short chain trans-2-enoyl-CoA reductase in the hepatic utilization of acetoacetyl-CoA and in the synthesis of butyryl-CoA for hepatic lipogenesis is discussed [8].
• The rate constant for reaction at 565 nm is approximately 12 s-1 ((butyryl-CoA) = 2.5 x 10(-5) M, pH 8.6), and the 450 nm rate profile can be fit to a rate equation for two sequential reactions of rate constant 12 s-1 and 3.4 s-1, the amount of flavin reduction in each kinetic step being approximately 50% [9].
• We have shown that we can produce butyryl-CoA at levels of up to 50% of the total CoA pool in Escherichia coli cells that overexpress the acetoacetyl-CoA:acetyl-CoA transferase, AtoAD (EC 2.8.3.8), in media supplemented with butyrate [10].

Chemical compound and disease context of butyryl-CoA

• The cDNA was expressed in eukaryotic (COS) and prokaryotic (Escherichia coli) cells, producing a protein of the expected size, with activity toward the short branched chain acyl-CoA derivatives ((S)-2-methylbutyryl-CoA, isobutyryl-CoA, and 2-methylhexanoyl-CoA), as well as toward the short straight chain acyl-CoAs (butyryl-CoA and hexanoyl-CoA) [11].
• NAD-independent lactate and butyryl-CoA dehydrogenases of Clostridium acetobutylicum P262 [12].
• When propionyl-CoA was substituted for either acetyl-CoA or butyryl-CoA in the presence of [14C]malonyl-CoA and NADPH, the pure human liver fatty acids synthetase complex synthesized only straight-chain, saturated, 15- and 17-carbon radioactive fatty acids [13].

Biological context of butyryl-CoA

• The active-site mutant Glu367Gln SCAD inactivates the reductive and oxidative pathways and allows the effects of substrate (butyryl-CoA) and product (crotonyl-CoA) binding on the redox properties of the Glu367Gln SCAD mutant protein to be determined separately [14].
• Accordingly the mitochondrial enzyme seems to be mainly responsible for the formation of free acetate by the intact liver, especially in view of the fact that the substrate specificity of the mitochondrial enzyme is much higher (activity ratios acetyl-CoA/butyryl-CoA 4.99 and 1.16 for the mitochondrial and the cold-labile enzyme respectively) [15].
• UV mutagenesis of S. cinnamonensis L1 and L1/pExIM1 led to mutants which were able to grow efficiently on acetate despite a block in the butyryl-CoA pathway [16].

Anatomical context of butyryl-CoA

• When short-chain fatty acids are metabolized by hepatocytes, AMP is readily formed within the matrix by the butyryl-CoA ligase (AMP-forming) reaction (EC 6.2.1.2) [17].
• Acetate utilization and butyryl coenzyme A (CoA):acetate-CoA transferase in butyrate-producing bacteria from the human large intestine [18].
• 3. Microsomal diacylglycerol acyltransferase from mammary gland and liver of non-ruminants was also capable of utilizing butyryl-CoA [19].
• In human skeletal muscle we also found low butyryl-CoA formation, which was limited to the mitochondrial matrix [20].
• Butyryl-CoA (C4:0) was not oxidized by purified peroxisomes [21].

Associations of butyryl-CoA with other chemical compounds

• The potential of the butyryl-CoA/crotonyl-CoA couple (E ' = -0.013 V) is significantly more positive than the potential of either of the enzymes with which it interacts, bacterial butyryl-CoA dehydrogenase (E ' = -0.079 V) and mammalian general acyl-CoA dehydrogenase (E ' = 0.133 V) [22].
• The DEBS polyketide synthase (PKS) used butyryl-CoA and methylmalonyl-CoA supplied in vivo by the AtoAD and methylmalonyl-CoA mutase pathways, respectively, to produce 15-methyl-6-dEB [10].
• Mechanism of action of glutaryl-CoA and butyryl-CoA dehydrogenases. Purification of glutaryl-CoA dehydrogenase [23].
• Additional in vivo incorporation studies with perdeuterated butyrate suggested that, in accord with the in vitro studies, the biosynthesis of the palmitate from butyryl-CoA decreases in the presence of thiolactomycin [24].
• The Km values at 30 degrees C and pH 8.0 for butyryl-CoA, phosphate, butyryl phosphate, and CoASH (reduced form of CoA) were 0.11, 14, 0.26, and 0.077 mM, respectively [25].

Gene context of butyryl-CoA

• We proposed that these results support an oxidation mechanism for glutaryl-CoA dehydrogenase and butyryl-CoA dehydrogenase which is initiated by proton abstraction [23].
• In addition, a site-directed Glu367 Gln mutant of SCAD expressed from a pUC119 vector was shown to have minimal reductive and oxidative pathway activity with butyryl-CoA and crotonyl-CoA, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)[26]
• Experimental evidence for the formation of a complex between butyryl coenzyme A dehydrogenase and the 'electron transferring flavoprotein', ETF [27].
• Crotonyl-CoA reductase (CCR) is a key enzyme in this pathway and catalyzes the last step of the conversion of 2-acetyl-CoA molecules to butyryl-CoA [16].

Analytical, diagnostic and therapeutic context of butyryl-CoA

• Since relatives of strain 49 (strains Nor37, PI-7, VV1, and OB156, based on 16S rRNA sequence analysis) all had the same method of butyrate production, it appeared that butyryl-CoA/acetate CoA transferase might be a phylogenetic characteristic [28].
• A similar titration with butyryl-CoA showed that reduction by this substrate was incomplete with 4.5 mol butyryl-CoA added per mol enzyme FAD; the equilibrium was used to calculate that the oxidation-reduction potential of the enzyme at pH 7 and 25 degrees C is 5+/-5 mV versus the standard hydrogen electrode [29].
• Butyryl-CoA synthetase extracted from untreated or freeze-dried liver mitochondria consisted of two fractions of Mr 40,000 and 46,000 as determined by gel permeation chromatography, the higher value being confirmed by sedimentation equilibrium [30].

References