Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:6.2.1.3 (acyl-CoA synthetase)
1,285 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. State-3 (i.e. ADP-stimulated) rates of O(2) uptake with palmitoylcarnitine, palmitoyl-CoA plus carnitine, pyruvate plus malonate plus carnitine and octanoate as respiratory substrate were all diminished in heart mitochondria isolated from senescent (24-month-old) rats compared with mitochondria from young adults (6 months old). By contrast, State-3 rates of O(2) uptake with pyruvate plus malate or glutamate plus malate were the same for mitochondria from each age group. 2. Measurements of enzyme activities in disrupted mitochondria showed a decline with senescence in the activity of acyl-CoA synthetase (EC 6.2.1.2 and 6.2.1.3), carnitine acetyltransferase (EC 2.3.1.7) and 3-hydroxy-acyl-CoA dehydrogenase (EC 1.1.1.35), but no change in the activity of carnitine palmitoyltransferase (EC 2.3.1.21) or acyl-CoA dehydrogenase (EC 1.3.99.3). 3. Measurement of dl-[(3)H]carnitine (in)/acetyl-l-carnitine (out) exchange in intact mitochondria showed decreased rates when the animals used were senescent. However, this followed from a decreased intramitochondrial pool of exchangeable carnitine, such that calculated first-order rate constants for exchange were identical in mitochondria from the two age groups. 4. The decline in acyl-CoA synthetase activity is thought to be the reason for the diminished rate of O(2) uptake with octanoate in senescence. The decline in carnitine acetyltransferase activity is considered to be the cause of the diminished rate of O(2) uptake with acetylcarnitine or with pyruvate plus malonate plus carnitine as substrate. The mechanism of the diminished rate of O(2) uptake with palmitoylcarnitine in senescence is discussed.
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PMID:Lipid oxidation by heart mitochondria from young adult and senescent rats. 63 43

In the enteric bacterium, Escherichia coli, acyl coenzyme A synthetase (fatty acid:CoA ligase (AMP-forming) EC 6.2.1.3) activates exogenous long-chain fatty acids concomitant with their transport across the inner membrane into metabolically active CoA thioesters. These compounds serve as substrates for acyl-CoA dehydrogenase in the first step in the process of beta-oxidation. The acyl-CoA synthetase structural gene, fadD, has been identified on clone 6D1 of the Kohara E. coli gene library and by a process of subcloning and complementation analyses shown to be contained on a 2.2-kilobase NcoI-ClaI fragment of genomic DNA. The polypeptide encoded within this DNA fragment was identified following T7 RNA polymerase-dependent induction and estimated to be M(r) = 62,000 using SDS-polyacrylamide gel electrophoresis. The N-terminal amino acid sequence of acyl-CoA synthetase was determined by automated sequencing to be Met-Lys-Lys-Val-Trp-Leu-Asn-Arg-Tyr-Pro. Sequence analysis of the 2.2-kilobase NcoI-ClaI fragment revealed a single open reading frame encoding these amino acids as the first 10 residues of a protein with a molecular weight of 62,028. The initiation codon for methionine was TTG. Primer extension of total in vivo mRNA from two fadD-specific oligonucleotides defined the transcriptional start at an adenine residue 60 base pairs upstream from the predicted translational start site. Two FadR operator sites of the fadD gene were identified at positions -13 to -29 (OD1) and positions -99 to -115 (OD2) by DNase I footprinting. Comparisons of the predicted amino acid sequence of the E. coli acyl-CoA synthetase to the deduced amino acid sequences of the rat and yeast acyl-CoA synthetases and the firefly luciferase demonstrated that these enzymes shared a significant degree of similarity. Based on the similar reaction mechanisms of these four enzymes, this similarity may define a region required for the same function.
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PMID:Cloning, sequencing, and expression of the fadD gene of Escherichia coli encoding acyl coenzyme A synthetase. 146 45

Syntrophomonas wolfei is an anaerobic fatty acid degrader that can only be grown in coculture with H2-using bacteria such as Methanospirillum hungatei. Cells of S. wolfei were selectively lysed by lysozyme treatment, and unlysed cells of M. hungatei were removed by centrifugation. The cell extract of S. wolfei obtained with this method had low levels of contamination by methanogenic cofactors. However, lysozyme treatment was not efficient in releasing S. wolfei protein; only about 15% of the L-3-hydroxyacyl-coenzyme A (CoA) dehydrogenase activity was found in the lysozyme supernatant. Cell extracts of S. wolfei obtained with this method had high specific activities of acyl-CoA dehydrogenase, enoyl-CoA hydratase, L-3-hydroxyacyl-CoA dehydrogenase, and 3-ketoacyl-CoA thiolase. These activities were not detected in cell extracts of M. hungatei grown alone, confirming that these activities were present in S. wolfei. The acyl-CoA dehydrogenase activity was high when a C4 but not a C8 or C16 acyl-CoA derivative served as the substrate. S. Wolfei cell extracts had high CoA transferase specific activities and no detectable acyl-CoA synthetase activity, indicating that fatty acid activation occurred by transfer of CoA from acetyl-CoA. Phosphotransacetylase and acetate kinase activities were detected in cell extracts of S. wolfei, indicating that S. wolfei is able to perform substrate-level phosphorylation.
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PMID:Preparation of cell-free extracts and the enzymes involved in fatty acid metabolism in Syntrophomonas wolfei. 345 26

We report the first direct measurement of delta-6 desaturase and delta-9 desaturase (EC 1.3.99.3, acyl-CoA dehydrogenase) activities in the rat kidney. Crude renal cortical homogenates from alloxan-diabetic and from normal rats were assayed for delta-6 and delta-9 desaturase activities. The delta-6 desaturation pathway activity measured with 9,12-octadecadienoic acid (linoleic acid) as substrate was increased, while the delta-9 desaturation pathway measured with hexadecanoic acid (palmitic acid) as substrate was unchanged in diabetic renal cortex, suggesting that the two enzymes are regulated independently in this tissue. In contrast to the kidney, delta-6 desaturase pathway activity was unchanged and the delta-9 desaturase pathway activity was greatly depressed in diabetic liver. When exogenous long-chain acyl-CoA synthetase (EC 6.2.1.3; acid: CoA ligase, AMP-forming) was added to the delta-6 desaturase assay system, the rate of delta-6 desaturation in normal kidney increased to a rate similar to that found in diabetic kidney; rates in diabetic extracts were unchanged. These results suggest that the rate of fatty acid substrate activation to the coenzyme A ester limits the rate of delta-6 desaturation in normal renal cortex. These results also suggest that the rate of fatty acid activation by long-chain acyl-CoA synthetase activity is increased in diabetic renal cortex. Direct measurement of the activity of long-chain acyl-CoA synthetase demonstrated that its activity was indeed increased significantly in the renal cortex of diabetic rats.
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PMID:Effects of diabetes mellitus on renal fatty acid activation and desaturation. 407 91

1. A study was made of the biodegradation of alkylbenzene sulphonate homologues, one of the major components of commercially marketed detergents. A Bacillus species was elected for growth on alkylbenzene sulphonate homologues as the sole source of carbon and sulphur. 2. The results from both whole-cell and cell-free systems indicated that the alkyl, aryl and sulphonate moieties of alkylbenzene sulphonate homologues were all further metabolized by the Bacillus species. 3. The alkyl side chain, after a presumed initial oxidation of the terminal methyl group, was subsequently oxidized by a beta-oxidation pathway. Three enzymes of the beta-oxidation pathway, i.e. acyl-CoA synthetase, acyl-CoA dehydrogenase and beta-hydroxyacyl-CoA dehydrogenase, were identified in cell-free extracts of the detergent-grown Bacillus species. The substrate specificity of acyl-CoA synthetase indicated activity towards several alkylbenzene sulphonate homologues. 4. The sulphonate moiety was released as sulphite by a desulphonating enzyme. Some kinetic properties of this enzyme were determined. The sulphite was subsequently metabolized to either sulphate or adenosine 5'-sulphatophosphate. Two enzymes involved in sulphite metabolism, i.e. sulphite-cytochrome c reductase and adenosine 5'-sulphatophosphate-cytochrome c reductase were detected in cell-free extracts of undecylbenzene-p-sulphonate-grown Bacillus species. 5. The combined results of continuous sampling programmes monitored by both t.l.c. and sulphite appearance in the growth medium indicated that desulphonation of the aromatic moiety was the likely first step in the overall biodegradation of several alkylbenzene sulphonate homologues. 6. The presence of p-hydroxyphenylpropionate, p-hydroxybenzoate and 3,4-dihydroxybenzoate in cells after growth on several alkylbenzene sulphonate homologues containing an odd number of carbon atoms in the side chain was confirmed by g.l.c. and t.l.c. analysis. Cells grown on several homologues containing an even number of carbon atoms in the side chain were shown to contain p-hydroxyphenylacetate and 3,4-dihydroxyphenylacetate. 7. The aromatic nucleus obtained from undecylbenzene-p-sulphonate was further metabolized by an oxidation sequence involving an ;ortho-cleavage' route. 8. An overall metabolic pathway for the biodegradation of various alkylbenzene sulphonate homologues by this Bacillus species is proposed.
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PMID:Microbial metabolism of alkylbenzene sulphonates. Bacterial metabolism of undecylbenzene-p-sulphonate and dodecylbenzene-p-sulphonate. 434 74

The acyl-CoA synthetase (acid: CoA ligase (AMP-forming), EC 6.2.1.3) activity of rat heart has been measured in fatty acid-depleted fractions of mitochondria, microperoxisomes and microsomes. The assay was based on (i) the measurement of the reaction product AMP by high-performance liquid chromatography or (ii) a coupled reaction in which the intramitochondrial (matrix) CoASH is the final acyl acceptor and the redox state of the flavoproteins in the acyl-CoA dehydrogenase pathway is used to determine the intramitochondrial level of acyl-CoA. This spectrophotometric method was also used to estimate the 'outer' carnitine long-chain acyltransferase (palmitoyl-CoA:L-carnitine O-palmitoyltransferase, EC 2.3.1.21) activity. Comparison of the distribution of long-chain acyl-CoA synthetase activity and marker enzymes in the various subcellular fractions revealed that the synthetase activity is exclusively localized in the mitochondrial fraction. Experimental evidence is presented in support of the conclusion that the chain-length specificity of saturated and monounsaturated fatty acids (16:1-22:1) for the acyl-CoA synthetase is mainly determined by the availability of the fatty acid at the active site, which is largely determined by the affinity of binding of fatty acids to the bulk phase of the mitochondrial phospholipids. Among the 22:1 isomers, 22:1(11) (cis) (cetoleic acid) revealed a slightly higher activity (1.4-fold) than 22:1(13) (cis) (erucic acid). The polyunsaturated fatty acids tested were rather poor substrates. Using isolated intact mitochondria and 16:0 or 22:1(13) (cis) as the substrates, it was found that the initial rate of the 'outer' long-chain acyltransferase activity was approximately four times higher than that of the long-chain acyl-CoA synthetase. The data support the hypothesis that the long-chain acyl-CoA synthetase reaction is rate-limiting in the sequence of coupled reactions leading to beta-oxidation in the mitochondrial matrix.
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PMID:Acyl-CoA synthetase activity of rat heart mitochondria. Substrate specificity with special reference to very-long-chain and isomeric fatty acids. 640 51

Effects of long-term administration of riboflavin, sodium butyrate or riboflavin 2',3',4',5'- tetrabutyrate ( RTB ) on the activities of renal and hepatic enzymes that catalyze the beta-oxidation of fatty acid were determined in the rat. Feeding of riboflavin or sodium butyrate for 5 weeks had no effect on all the enzymes examined. By contrast, feeding of RTB resulted in an increase in the hepatic activity of 3-ketoacyl-CoA thiolase [EC 2.3.1.16] by 50% of the control level, while the activities of renal 3-ketoacyl-CoA thiolase and of hepatic and renal acyl-CoA synthetase [EC 6.2.1.3] and acyl-CoA dehydrogenase [EC 1.3.99.3] remained unaffected. The increase in hepatic 3-ketoacyl-CoA thiolase activity suggests that prolonged RTB administration results in an increased beta-oxidation of fatty acid in the liver, which may explain the reported reduction in the concentration of tryglyceride in plasma during RTB treatment.
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PMID:Effect of chronic administration of riboflavin 2',3',4',5'-tetrabutyrate on the hepatic enzymes of fatty acid oxidation in the rat. 667 46

Rats were maintained on fat-free high carbohydrate diets either with or without orotic acid (1%, w/w), pantethine (1%, w/w), adenine (0.25%, w/w), and/or p-chlorophenoxyisobutyrate (0.25%, w/w). Oxidation of fatty acid by liver mitochondria was inhibited to less than half that of the control after administration of orotic acid. Activities of acyl-CoA dehydrogenases were markedly decreased by orotic acid administration, but the following enzyme activities were not, or only slightly decreased: acyl-CoA synthetase, carnitine acyltransferases, enoyl-CoA hydratase, 3-hydroxyacyl-CoA dehydrogenase and 3-ketoacyl-CoA thiolase. Simultaneous addition of pantethine in the orotic acid-containing diet prevented induction of fatty liver. It also prevented decreases in fatty acid oxidation capacity and acyl-CoA dehydrogenase activity. Introduction of adenine or p-chlorophenoxyisobutyrate, which reverse orotic acid-induced fatty liver, reversed oxidation and acyl-CoA dehydrogenase activities to control levels. The oxidation capacity of the peroxisomal system remained unchanged after administration of orotic acid.
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PMID:Reduction of beta-oxidation capacity of rat liver mitochondria by feeding orotic acid. 710 78

Galactomyces reessii accomplishes the enzymatic transformation of beta-methylbutyric acid (isovaleric acid) to beta-hydroxy-beta-methylbutyric acid. The enzymatic basis for this bioconversion was evaluated by analyzing cell-free extracts of G. reessii for enzyme activities commonly associated with leucine catabolism. G. reessii extracts contained activities for acyl-CoA synthetase, acyl-CoA dehydrogenase, and enoyl-CoA hydratase, whereas beta-methylbutyric acid hydroxylase, alpha-ketoisocaproate oxygenase, and acyl-CoA oxidase (with isovaleryl-CoA as substrate) were not observed. Furthermore, beta-methylbutyric acid is initially activated to isovaleryl-CoA by acyl-CoA synthetase, dehydrogenated to methylcrotonyl-CoA by acyl-CoA dehydrogenase, hydrated to beta-hydroxy-beta-methylbutyric acid-CoA by enoyl-CoA hydratase, and hydrolyzed to beta-hydroxy-beta-methylbutyric acid in G. reessii extracts. Cell-free extracts converted both isovaleryl-CoA and methylcrotonyl-CoA into beta-hydroxy-beta-methylbutyric acid, thus demonstrating that beta-methylbutyric acid is part of the leucine catabolic pathway. The rate of beta-methylbutyric acid conversion to beta-hydroxy-beta-methylbutyric acid with cell-free extract was 0. 013 &mgr;mol beta-hydroxy-beta-methylbutyric acid (mg protein)-1 h-1, while the conversion rate of leucine was fivefold lower. With whole cells, the highest production rate [0.042 &mgr;mol beta-hydroxy-beta-methylbutyric acid (g cells)-1 h-1] was also observed with beta-methylbutyric acid. The results indicate that beta-methylbutyric acid is transformed to beta-hydroxy-beta-methylbutyric acid through the leucine catabolic pathway.
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PMID:Enzyme analyses demonstrate that beta-methylbutyric acid is converted to beta-hydroxy-beta-methylbutyric acid via the leucine catabolic pathway by galactomyces reessii 947 61

In mice and other sensitive species, PPARalpha mediates the induction of mitochondrial, microsomal, and peroxisomal fatty acid oxidation, peroxisome proliferation, liver enlargement, and tumors by peroxisome proliferators. In order to identify PPARalpha-responsive human genes, HepG2 cells were engineered to express PPARalpha at concentrations similar to mouse liver. This resulted in the dramatic induction of mRNAs encoding the mitochondrial HMG-CoA synthase and increases in fatty acyl-CoA synthetase (3-8-fold) and carnitine palmitoyl-CoA transferase IA (2-4-fold) mRNAs that were dependent on PPARalpha expression and enhanced by exposure to the PPARalpha agonist Wy14643. A PPAR response element was identified in the proximal promoter of the human HMG-CoA synthase gene that is functional in its native context. These data suggest that humans retain a capacity for PPARalpha regulation of mitochondrial fatty acid oxidation and ketogenesis. Human liver is refractory to peroxisome proliferation, and increased expression of mRNAs for the peroxisomal fatty acyl-CoA oxidase, bifunctional enzyme, or thiolase, which accompanies peroxisome proliferation in responsive species, was not evident following Wy14643 treatment of cells expressing elevated levels of PPARalpha. Additionally, no significant differences were seen for the expression of apolipoprotein AI, AII, or CIII; medium chain acyl-CoA dehydrogenase; or stearoyl-CoA desaturase mRNAs.
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PMID:Identification of peroxisome proliferator-responsive human genes by elevated expression of the peroxisome proliferator-activated receptor alpha in HepG2 cells. 1137 53


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