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:6.2.1.1 (ACS)
78,556 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Acetyl CoA synthetase (ACS; EC 6.2.1.1) was studied in the mosquito, Aedes togoi, by a novel assay which coupled the acetyl-CoA generated to p-aminosalicylic acid (ASA). The N-acetylated product was determined by an HPLC-fluorimetric procedure. High ACS activity was observed in the newly-pupated pupae of both sexes and in the adult male mosquito whose activity was five times that of the female. Acetyl CoA-dependent N-acetyltransferase (NAT; EC 2.3.1.5) activity toward serotonin (5HT) was also studied using HPLC-electrochemical detection (HPLC-ECD). A progressive increase in the 5HT-NAT activity was observed from the fourth-instar larvae to the adult mosquito with the latter showing 6-fold higher activity in the head compared to the abdomen-thorax region. Kinetic studies on the pupal enzyme extracts showed that the apparent Km values for 5HT and acetyl CoA were 63 and 66 microM respectively. Tryptamine inhibited 5HT-NAT non-competitively with a Ki value of 8 microM.
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PMID:Acetyl CoA generation and N-acetylation of serotonin (5HT) in the mosquito, Aedes togoi. 791 72

Saccharomyces cerevisiae T23C (pda1::Tn5ble) is an isogenic gene replacement mutant of the wild-type strain S. cerevisiae T23D. The mutation causes a complete loss of pyruvate dehydrogenase activity. Pyruvate metabolism in this pyruvate-dehydrogenase-negative (Pdh-) strain was investigated in aerobic glucose-limited chemostat cultures, grown at a dilution rate of 0.10 h-1, and compared with the metabolism in the isogenic wild-type strain. Under these conditions, growth of the Pdh- strain was fully respiratory. Enzyme activities in cell-free extracts indicated that the enzymes pyruvate decarboxylase, acetaldehyde dehydrogenase and acetyl-coenzyme A (acetyl-CoA) synthetase could provide a functional bypass of the pyruvate dehydrogenase complex. Since this metabolic sequence involves ATP hydrolysis in the acetyl-CoA synthetase reaction, a negative effect of the pda1::Tn5ble mutation on the growth efficiency was anticipated. Indeed, the biomass yield of the Pdh- strain [0.44 g biomass (g glucose)-1] was significantly lower than that of wild-type S. cerevisiae [0.52 g biomass (g glucose)-1]. The effect of the mutation on biomass yield could be quantitatively explained in terms of a lower ATP yield from glucose catabolism and an increased ATP requirement for the synthesis of acetyl-CoA used in anabolism. Control experiments showed that the pda1::Tn5ble mutation did not affect biomass yield in ethanol-limited chemostat cultures. The results support the view that, during aerobic glucose-limited growth of S. cerevisiae at low growth rates, the pyruvate dehydrogenase complex accounts for the major part of the pyruvate flux. Moreover, it is concluded that hydrolysis of pyrophosphate formed in the acetyl-CoA synthetase reaction does not contribute significantly to energy transduction in this yeast. Respiratory-deficient cells did not contribute to glucose metabolism in the chemostat cultures and were probably formed upon plating.
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PMID:Energetic aspects of glucose metabolism in a pyruvate-dehydrogenase-negative mutant of Saccharomyces cerevisiae. 801 82

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.
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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.
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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.
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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.
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PMID:Purification and characterization of the acetate forming enzyme, acetyl-CoA synthetase (ADP-forming) from the amitochondriate protist, Giardia lamblia. 855 9

The three types of peroxisome proliferator activated receptor (PPAR), alpha, beta (or delta), and gamma, each with a specific tissue distribution, compose a subfamily of the nuclear hormone receptor gene family. Although peroxisome proliferators, including fibrates and fatty acids, activate the transcriptional activity of these receptors, only prostaglandin J2 derivatives have been identified as natural ligands of the PPAR gamma subtype, which also binds thiazolidinedione antidiabetic agents with high affinity. Activated PPARs heterodimerize with RXR and alter the transcription of target genes after binding to specific response elements or PPREs, consisting of a direct repeat of the nuclear receptor hexameric DNA core recognition motif spaced by one nucleotide. The different PPARs can be considered key messengers responsible for the translation of nutritional, pharmacological and metabolic stimuli into changes in the expression of genes, more specifically those genes involved in lipid metabolism. PPAR alpha is involved in stimulating beta-oxidation of fatty acids. In rodents, a PPAR alpha-mediated change in the expression of genes involved in fatty acid metabolism lies at the basis of the phenomenon of peroxisome proliferation, a pleiotropic cellular response, mainly limited to liver and kidney and which can lead to hepatocarcinogenesis. In addition to their role in peroxisome proliferation in rodents, PPAR is also involved in the control of HDL cholesterol levels by fibrates and fatty acids in rodents and humans. This effect is, at least partially, based on a PPAR-mediated transcriptional regulation of the major HDL apolipoproteins, apo A-I and apo A-II. The hypotriglyceridemic action of fibrates and fatty acids also involves PPARs and can be summarized as follows: (1) an increased lipolysis and clearance of remnant particles, due to changes in LPL and apo C-III levels, (2) a stimulation of cellular fatty acid uptake and their conversion to acyl-CoA derivatives by the induction of FAT, FATP and ACS activity, (3) an induction of fatty acid beta-oxidation pathways, (4) a reduction in fatty acid and triglyceride synthesis, and finally (5) a decrease in VLDL production. Hence, both enhanced catabolism of triglyceride-rich particles as well as reduced secretion of VLDL particles are mechanisms that contribute to the hypolipidemic effect of fibrates and FFAs. Whereas for PPAR beta no function so far has been identified, PPAR gamma triggers adipocyte differentiation by inducing the expression of several genes critical for adipogenesis.
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PMID:The peroxisome proliferator activated receptors (PPARS) and their effects on lipid metabolism and adipocyte differentiation. 869 69

Carbon monoxide is produced by several biological reactions. It is proposed to act as an intracellular signaling molecule and can serve as the carbon and electon source for certain bacteria. Direct evidence for a new biological role for CO is presented here. The results strongly indicate that CO is produced as an obligatory intermediate during growth of the acetogenic bacterium Clostridium thermoaceticum on glucose, H2/CO2, or aromatic carboxylic acids. Our results are consistent with earlier hypotheses of the intermediacy of CO during growth of acetogenic bacteria on CO2 and hexoses [Diekert, G., & Ritter, M. (1983) FEMS Microbiol. Lett. 17, 299-302] and methanogenic Archaea on CO2 [Stupperich, E., Hammel, K. E., Fuchs, G., & Thauer, R. K. (1983) FEBS Lett. 152, 21-23]. Therefore, CO production is a key step in the Wood-Ljungdahl pathway of acetyl-CoA synthesis. The carbonyl group of acetyl-CoA is shown to be formed from the carboxyl group of pyruvate by the following steps. (i) Pyruvate undergoes decarboxylation by pyruvate:ferredoxin oxidoreductase to form acetyl-CoA and CO2. (ii) CO2 is reduced to CO by the CODH site of the bifunctional enzyme CO dehydrogenase/acetyl-CoA synthase (CODH/ACS). (iii) CO generated in situ combines with the ACS active site to form a paramagnetic adduct that has been called the NiFeC species, and (iv) the bound carbonyl group combines with a bound methyl group and CoA to generate acetyl-CoA. To our knowledge, this paper represents the first demonstration of a pathway in which CO is produced and then used as a metabolic intermediate.
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PMID:Evidence that carbon monoxide is an obligatory intermediate in anaerobic acetyl-CoA synthesis. 881 Sep 18

Pyrococcus furiosus is a strictly anaerobic archaeon (archaebacterium) that grows at temperatures up to 105 degrees C by fermenting carbohydrates and peptides. Cell extracts have been previously shown to contain an unusual acetyl coenzyme A (acetyl-CoA) synthetase (ACS) which catalyzes the formation of acetate and ATP from acetyl-CoA by using ADP and phosphate rather than AMP and PPi. We show here that P. furiosus contains two distinct isoenzymes of ACS, and both have been purified. One, termed ACS I, uses acetyl-CoA and isobutyryl-CoA but not indoleacetyl-CoA or phenylacetyl-CoA as substrates, while the other, ACS II, utilizes all four CoA derivatives. Succinyl-CoA did not serve as a substrate for either enzyme. ACS I and ACS II have similar molecular masses (approximately 140 kDa), and both appear to be heterotetramers (alpha2beta2) of two different subunits of 45 (alpha) and 23 (beta) kDa. They lack metal ions such as Fe2+, Cu2+, Zn2+, and Mg2+ and are stable to oxygen. At 25 degrees C, both enzymes were virtually inactive and exhibited optimal activities above 90 degrees C (at pH 8.0) and at pH 9.0 (at 80 degrees C). The times required to lose 50% of their activity at 80 degrees C were about 18 h for ACS I and 8 h for ACS II. With both enzymes in the acid formation reactions, ADP and phosphate could be replaced by GDP and phosphate but not by CDP and phosphate or by AMP and PPi. The apparent Km values for ADP, GDP, and phosphate were approximately 150, 132, and 396 microM, respectively, for ACS I (using acetyl-CoA) and 61, 236, and 580 microM, respectively, for ACS II (using indoleacetyl-CoA). With ADP and phosphate as substrates, the apparent Km values for acetyl-CoA and isobutyryl-CoA were 25 and 29 microM, respectively, for ACS I and 26 and 12 microM, respectively, for ACS II. With ACS II, the apparent Km value for phenylacetyl-CoA was 4 microM. Both enzymes also catalyzed the reverse reaction, the ATP-dependent formation of the CoA derivatives of acetate (I and II), isobutyrate (I and II), phenylacetate (II only), and indoleacetate (II only). The N-terminal amino acid sequences of the two subunits of ACS I were similar to those of ACS II and to that of a hypothetical 67-kDa protein from Escherichia coli but showed no similarity to mesophilic ACS-type enzymes. To our knowledge, ACS I and II are the first ATP-utilizing enzymes to be purified from a hyperthermophile, and ACS II is the first enzyme of the ACS type to utilize aromatic CoA derivatives.
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PMID:Purification and characterization of two reversible and ADP-dependent acetyl coenzyme A synthetases from the hyperthermophilic archaeon Pyrococcus furiosus. 883 Jun 84

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.
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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


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