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

---

Query: EC:6.2.1.13 (acetyl-CoA synthetase)
451 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The time-course of ketone body concentrations, the activities of enzymes of their utilization as well as the activities of acetyl-CoA synthetase and ATP-citrate lyase were studied in the liver, brain and heart of rats receiving ethanol for 40 days (3 g/kg, intragastrally). Ethanol increased the concentration of 3-hydroxybutyrate 3 hr following the last ethanol treatment in the blood and tissues investigated and that of acetoacetate in the liver with raised acetoacetyl-CoA synthetase activity in all three tissues. The activities of acetyl-CoA-generating enzymes were, however, increased only in the liver and heart. Chronic alcohol intoxication diminished the activities of ketone body utilizing enzymes (3-hydroxybutyrate dehydrogenase and 3-oxo acid-CoA transferase) in the heart but not in the brain. The data obtained indicate both disturbed ketone body utilization and increased importance of acetate produced from ethanol as an energy source in the heart during long-term ethanol treatment.
...
PMID:Utilization of ketone bodies by the rat liver, brain and heart in chronic alcohol intoxication. 810

Oxidative metabolism in the in vivo canine myocardium was studied noninvasively using 13C-enriched acetate and non-steady state 13C NMR techniques. Under low workload conditions, the myocardium oxidized the infused [2-13C]acetate and incorporated the labeled carbon into the glutamate pool as expected. This conclusion stems from the rapid enrichment of the C-2, C-3, and C-4 carbons of glutamic acid both under in vivo conditions and in extracts. Surprisingly, [2-13C]acetate uptake was not observed at high workloads as reflected by an absence of glutamate pool enrichment at these rate pressure products. Rather, the myocardium selected its substrate from an endogenous pool. Since free acetate can directly cross the inner mitochondrial membrane and be converted to acetyl-CoA through acetyl-CoA synthetase, these results support workload-dependent regulation of substrate access to the mitochondrial CoASH pool. As such, we advance the hypothesis that the selection of substrate for condensation with CoASH and subsequent oxidation in the tricarboxylic acid cycle is regulated kinetically through the Km values of the appropriate condensation enzymes and through the absolute levels of free CoASH in the mitochondria.
...
PMID:Dynamic 13C NMR analysis of oxidative metabolism in the in vivo canine myocardium. 825 51

The mutant gene coding for a proline-activating domain (grs2-pro) was cloned and sequenced from Bacillus brevis Nagano, BII-3 strain, which produces gramicidin S synthetase 2 defective in proline-activation. By comparison of the nucleotide sequence with the wild-type sequence, a single point mutation was found at the 2609th guanine, which was replaced with adenine, resulting in the change of the 870th glycine to glutamic acid. Homology search for the deduced amino acid sequence of grs2-pro gene revealed that the 870th glycine was conserved in adenylate-forming enzymes, and its flanking sequence was highly conserved among the aminoacyl adenylate-forming enzymes, such as antibiotic peptide synthetases: gramicidin S synthetase 1 and 2 (GS1, GS2), tyrocidine synthetase 1 (TS1), and delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine synthetase (ACVS); and other aminoacyl adenylation enzymes: alpha-aminoadipate reductase (LYS2), EntF, and AngR. On the other hand, this flanking sequence was not conserved in the other adenylate-forming enzymes lacking amino acid activation, such as acetyl-CoA synthetase, long-chain acyl-CoA synthetase, luciferase, and 4-coumarate CoA ligase. Single base substitutions at the 870th GGG codon were carried out by oligonucleotide site-directed mutagenesis. Four mutagenized clones were isolated, containing grs2-pro genes which exchange 870-Gly for alanine, valine, arginine, and tryptophan. The translated products from these clones could scarcely catalyze proline-dependent ATP-32PPi exchange reaction. The coil structure of 870-Gly region was lost in the mutants. These results suggest that the 870-Gly residue of grs2-pro protein is essential for aminoacyl-adenylation in the antibiotic peptide synthetase family.
...
PMID:Effect of single base substitutions at glycine-870 codon of gramicidin S synthetase 2 gene on proline activation. 827 62

Giardia lamblia, an amitochondriate eukaryote, contains acetyl-CoA synthetase (ADP-forming), an enzyme known only from one other eukaryote (Entamoeba histolytica) and a few anaerobic prokaryotes. The enzyme has been purified about 350-fold. The activity in the direction of acetate formation was dependent on ADP and inorganic phosphate. The reverse reaction could not be detected. Succinyl-CoA, propionyl-CoA and dADP were utilized with lower efficiency. The enzyme did not utilize AMP plus PPi thus differs from the broadly distributed acetyl-CoA synthetase (AMP-forming). The enzyme is responsible for acetate production accompanied by ATP generation, thus plays an important role in G. lamblia metabolism.
...
PMID:Purification and characterization of the acetate forming enzyme, acetyl-CoA synthetase (ADP-forming) from the amitochondriate protist, Giardia lamblia. 855 9

Two independent pathways in Escherichia coli convert acetate to acetyl CoA: reversal of acetate production by phosphotransacetylase and acetate kinase, and the acetyl-CoA synthetase (Acs) pathway that scavenges acetate. We investigated acs gene expression by using a cat transcriptional fusion. It was observed that acs expression varies depending on the carbon sources used and occurs in the stationary phase of growth even in the absence of acetate. Mutations in iclR for the repressor of the glyoxylate shunt and in rpoS for the stationary phase sigma factor reduced the consumption of acetate mediated by Acs, indicating that both are involved in acs regulation.
...
PMID:Involvement of iclR and rpoS in the induction of acs, the gene for acetyl coenzyme A synthetase of Escherichia coli K-12. 899 13

Acetyl-CoA synthetase (ADP-forming) is an enzyme in Archaea that catalyzes the formation of acetate from acetyl-CoA and couples this reaction with the synthesis of ATP from ADP and Pi (acetyl-CoA + ADP + Pi --> acetate + ATP + CoA) [Schifer, T., Selig, M. & Schonheit, P. (1993) Arch. Microbiol. 159, 72-83]. The enzyme from the anaerobic hyperthermophile Pyrococcus furiosus was purified 96-fold with a yield of 20% to apparent electrophoretic homogeneity. The oxygen-stable enzyme had an apparent molecular mass of 145 kDa and was composed of two subunits with apparent molecular masses of 47 kDa and 25 kDa, indicating an alpha2beta2 structure. The N-terminal amino acid sequences of both subunits were determined; they do not show significant identity to other proteins in databases. The purified enzyme catalyzed the reversible conversion of acetyl-CoA, ADP and Pi to acetate, ATP and CoA. The apparent Vmax value in the direction of acetate formation was 18 U/mg (55 degrees C), the apparent Km values for acetyl-CoA, ADP and Pi were 17 microM, 60 microM and 200 microM, respectively. ADP and Pi could not be replaced by AMP and PPi, defining the enzyme as an ADP-forming rather than an AMP-forming acetyl-CoA synthetase. The apparent Vmax value in the direction of acetyl-CoA formation was about 40 U/mg (55 degrees C), and the apparent Km values for acetate, ATP and CoA were 660 microM, 80 microM and 30 microM, respectively. The purified enzyme was not specific for acetyl-CoA or acetate, in addition to acetyl-CoA (100%), the enzyme accepts propionyl-CoA (110%) and butyryl-CoA (92%), and in addition to acetate (100%), the enzyme accepts propionate (100%), butyrate (92%), isobutyrate (79%), valerate (36%) and isovalerate (34%), indicating that the enzyme functions as an acyl-CoA synthetase (ADP-forming) with a broad substrate spectrum. Succinate, phenylacetate and indoleacetate did not serve as substrates for the enzyme (<3%). In addition to ADP (100%), GDP (220%) and IDP (250%) were used, and in addition to ATP (100%), GTP (210%) and ITP (320%) were used. Pyrimidine nucleotides were not accepted. The enzyme was dependent on Mg2+, which could be partly substituted by Mn2+ and Co2+. The pH optimum was pH 7. The enzyme has a temperature optimum at 90 degrees C, which is in accordance with its physiological function under hyperthermophilic conditions. The enzyme was stabilized against heat inactivation by salts. In the presence of KCI (1 M), which was most effective, the enzyme did not loose activity after 2 h incubation at 100 degrees C.
...
PMID:Purification and properties of acetyl-CoA synthetase (ADP-forming), an archaeal enzyme of acetate formation and ATP synthesis, from the hyperthermophile Pyrococcus furiosus. 911 24

Concentrations of total CoAs in chloroplasts freshly isolated from spinach and peas were 10-20 microM, assuming a stromal volume of 66 microl per mg of chlorophyll. Acetyl-CoA and CoASH constituted at least 90% of the total CoA in freshly isolated chloroplasts. For a given chloroplast preparation, the concentration of endogenous acetyl-CoA was the same when extractions were performed using HClO4, trichloroacetic acid, propan-2-ol or chloroform/methanol, and the extracts analysed by quantitative HPLC after minimal processing. During fatty acid synthesis from acetate, concentrations of CoASH within spinach and pea chloroplasts varied from less than 0.1 to 5.0 microM. Malonyl-CoA concentrations were also very low (<0.1-3.0 microM) during fatty acid synthesis but could be calculated from radioactivity incorporated from [1-14C]acetate. Concentrations of CoASH in chloroplasts synthesizing fatty acids could be doubled in the presence of Triton X-100, suggesting that the detergent stimulates fatty acid synthesis by increasing the turnover rate of acyl-CoA. However, although taken up, exogenous CoASH (1 microM) did not stimulate fatty acid synthesis by permeabilized spinach chloroplasts. Calculated rates for acetyl-CoA synthetase, acetyl-CoA carboxylase and malonyl-CoA-acyl-carrier protein transacylase reactions at the concentrations of metabolites measured here are < 0.1-4% of the observed rates of fatty acid synthesis from acetate by isolated chloroplasts. The results suggest that CoA and its esters are probably confined within, and channelled through, the initial stages of a fatty acid synthase multienzyme complex.
...
PMID:Stromal concentrations of coenzyme A and its esters are insufficient to account for rates of chloroplast fatty acid synthesis: evidence for substrate channelling within the chloroplast fatty acid synthase. 935 62

The superfamily of adenylate forming enzymes including peptide synthetases, acyl-CoA synthetases and insect luciferases is readily identified by the signature sequence SGTTGXPKG. This sequence including an invariant lysyl residue is located in a disordered loop region and was predicted to be of significant antigenicity. Antibodies were generated employing YTSGTTGRPKGC attached to bovine serum albumin and have been successfully used to identify respective enzymes and adenylate forming domains in multienzyme systems. These include the delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine synthetases of Aspergillus nidulans and Acremonium chrysogenum, gramicidin S synthetase 1 and tyrocidine synthetase 1 from Bacillus brevis, acetyl-CoA synthetase from Alcaligenes eutrophus and a putative peptide synthetase from Metarhizium anisopliae. Weaker or no reactions are observed when the amino acid in position X in the protein is non-basic or hydrophobic, which is respectively the case for gramicidin S synthetase 1 and luciferase.
...
PMID:Group specific antibodies against the putative AMP-binding domain signature SGTTGXPKG in peptide synthetases and related enzymes. 953 May 7

Purified recombinant poly(hydroxyalkanoic acid), PHA, synthase from Chromatium vinosum was used to examine in vitro poly(3-hydroxybutyric acid) (P(3HB)) formation. In combination with purified propionyl-coenzyme A transferase of Clostridium propionicum a two-enzyme in vitro P(3HB) biosynthesis system was established which allowed the synthesis of P(3HB) from free D-(-)-3-hydroxybutyric acid as substrate. The coenzyme A residue for the activation of this hydroxyacid was provided by acetyl-coenzyme A. By adding acetyl-coenzyme A synthetase to this system, a three-enzyme in vitro P(3HB) biosynthesis system was established. Coenzyme A that was released during the polymerization reaction was coupled to acetate which again served as the coenzyme A donor for the activation of 3-hydroxybutyric acid. The energy for the in vitro P(3HB) synthesis was provided by ATP hydrolyses resulting in acetyl-coenzyme A synthesis catalyzed by the acetyl coenzyme A synthetase. In this way the in vitro synthesis of P(3HB) became independent of the consumption of the expensive coenzyme A. By this procedure a handy system is available to produce in vitro PHA on a semipreparative scale.
...
PMID:In vitro synthesis of poly(3-hydroxybutyric acid) by using an enzymatic coenzyme A recycling system. 983 44

A Giardia lamblia gene, Glacs, was cloned, sequenced and expressed in Escheria Coli. This gene codes for a 726 residue long acetyl-CoA synthetase (ADP-forming). This enzyme is responsible for the formation of acetate, a metabolic endproduct of G. lamblia. It is known from only two Type I amitochondriate eukaryotes, G. lamblia and Entamoeba histolytica and from the archaebacterium, Pyrococcus furiosus. With Glacs as query, homologous unidentified open reading frames were detected in the complete genomes of only a few archaebacteria and eubacteria. These form a new protein family present in all three domains of life, which probably plays a central role in the acyl-CoA metabolism but is of restricted taxonomic distribution.
...
PMID:Cloning and sequencing of an acetyl-CoA synthetase (ADP-forming) gene from the amitochondriate protist, Giardia lamblia. 1037 39


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---