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)

Strains of Escherichia coli lacking all cytoplasmic chemotaxis proteins except CheY swim smoothly under most conditions. However, they tumble when exposed to acetate. Acetate coenzyme A synthetase (EC 6.2.1.1) was thought to be essential for this response. New evidence suggests that the tumbling is mediated instead by acetate kinase (EC 2.7.2.1), which might phosphorylate CheY via acetyl phosphate. In strains that were wild type for chemotaxis, neither acetate coenzyme A synthetase, acetate kinase, nor phosphotransacetylase (EC 2.3.1.8) (and thus acetyl phosphate) was required for responses to aspartate, serine, or sugars sensed by the phosphotransferase system. Thus, acetate-induced tumbling does not appear to play an essential role in chemotaxis in wild-type cells.
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PMID:Change in direction of flagellar rotation in Escherichia coli mediated by acetate kinase. 809 30

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

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

The amebicidal action of metronidazole is activated when the enzyme pyruvate:ferredoxin oxido-reductase transfers reducing equivalents to the nitro group of the drug. The enzyme is present in Entamoeba histolytica and other anaerobic parasites like Giardia and Trichomonas that lack mitochondria. The selectivity of the drug can be ascribed to the absence of the reductase in the human host. E. histolytica possesses other enzymes involved in glucose catabolism that are interesting for the rational design of new drugs. It has glycolytic enzymes that are important for the production of energy like phosphofructokinase, pyruvate phosphate dikinase, phosphoenolpyruvate carboxytransphosphorylase and acetate thiokinase, which use pyrophosphate as a phosphate donor and have no human counterparts. The first part of this article describes the reactions by which E. histolytica obtains energy from glucose degradation, and includes recent advances in the cloning of genes for the various participating enzymes. The second part shows an alternative view for the study of target enzymes that are unique to the parasite, and indicates their importance in therapeutic research.
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PMID:Energy production in Entamoeba histolytica: new perspectives in rational drug design. 885 80

This paper describes a spectrophotometric assay that can measure the inorganic pyrophosphate produced from various enzymatic reactions. This is a coupled assay in which the addition of inorganic pyrophosphatase initially cleaves the pyrophosphate into two molecules of phosphate. The phosphate is then detected by the conversion of 2-amino-6-mercapto-7-methylpurine ribonucleoside to 2-amino-6-mercapto-7-methylpurine by purine nucleoside phosphorylase [M.R. Webb (1992) Proc. Natl. Acad. Sci. USA 89, 4884-4887]. The reaction is monitored by measuring the increase in absorbance at 360 nm. The generation of two molecules of phosphate from each molecule of pyrophosphate increases the sensitivity of the assay, which has a linear range from about 1 to 75 nmol pyrophosphate in a 1-ml reaction volume. To demonstrate the general usefulness of this assay, we show that the inorganic pyrophosphate generated by reactions involving acetyl-CoA synthetase and luciferase can be readily detected and that continuous as well as end-point assays can be performed.
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PMID:A spectrophotometric method to measure enzymatic activity in reactions that generate inorganic pyrophosphate. 895 23

The filamentous fungus Aspergillus nidulans is able to grow on phenylacetic acid (PhAc) as the sole carbon source and has a highly specific phenylacetic acid transport system mediating the uptake of this aromatic compound. This transport system is also able to transport some phenoxyacetic acid (PhOAc), although less efficiently. Maximal uptake rates were observed at 37 degrees C in 50 mM phosphate buffer (pH 7.0). Under these conditions, uptake was linear for at least 1 minute, with K(m) values for PhAc and PhOAc of 74 and 425 microM, respectively. The PhAc transport system is strongly induced by PhAc and, to a lesser extent by PhOAc and other phenyl derivatives. The utilization of glucose (and other sugars), glycerol or acetate results in a substantially reduced uptake. This negative effect caused by certain carbon sources is independent of the creA gene, the regulatory gene mediating carbon catabolite repression. Negative regulation by acetate is prevented by a loss-of-function mutation in the gene encoding acetyl-CoA synthetase, strongly suggesting that this regulation is mediated by the intracellular pool of acetyl-CoA.
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PMID:The phenylacetic acid uptake system of Aspergillus nidulans is under a creA-independent model of catabolic repression which seems to be mediated by acetyl-CoA. 906 65

Zygosaccharomyces bailii ISA 1307 displays biphasic growth in a medium containing a mixture of glucose (0.5%, w/v) and acetic acid (0.5%, w/v), pH 5.0 and 3.0. In cells harvested during the first growth phase, no activity of a mediated acetic acid transport system was found. Incubation of these cells in phosphate buffer with cycloheximide for 1 h restored activity of an acetic acid carrier which behaved as the one present in glucose-grown cells. These results indicated that the acetic acid carrier is probably present in cells from the first growth phase of the mixed medium but its activity was affected by the presence of acetic acid in the culture medium. In glucose-grown cells, after incubation in phosphate buffer with glucose and acetic acid, the activity of the acetic acid carrier decreased significantly with increased acid concentration in the incubation buffer. At acid concentrations above 16.7 mM, no significant carrier activity was detectable. Furthermore, the intracellular acid concentration increased with the extracellular one and was inversely correlated with the activity of the acetic acid carrier, suggesting the involvement of a feedback inhibition mechanism in the regulation of the carrier. During biphasic growth, the first phase corresponded to a simultaneous consumption of glucose and acetic acid, and the second to the utilization of the remaining acid. The enzyme acetyl-CoA synthetase was active in both growth phases, even in the presence of glucose. Activity of isocitrate lyase and phosphoenolpyruvate carboxykinase was found only in acetic-acid-grown cells. Thus it appears that both membrane transport and acetyl-CoA synthetase and their regulation are important for Z. bailii to metabolize acetic acid in the presence of glucose. This fact correlates with the high resistance of this yeast to environments with mixtures of sugars and acetic acid such as those often present during wine fermentation.
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PMID:Mechanisms underlying the transport and intracellular metabolism of acetic acid in the presence of glucose in the yeast Zygosaccharomyces bailii. 958 Mar 46

The hyperthermophilic, sulfate-reducing archaeon Archaeoglobus fulgidus strain 7324, rather than the type strain VC16, was found to grow on starch and sulfate as energy and carbon source. Fermentation products and enzyme activities were determined in starch-grown cells and compared to those of cells grown on lactate and sulfate. During exponential growth on starch, 1 mol of glucose-equivalent was incompletely oxidized with sulfate to approximately 2 mol acetate, 2 mol CO2 and 1 mol H2S. Starch-grown cells did not contain measurable amounts of the deazaflavin factor F420 (<0.03 nmol/mg protein) and thus did not show the F420-specific green-blue fluorescence. In contrast, lactate (1 mol) was completely oxidized with sulfate to 3 mol CO2 by strain 7324, and lactate-grown cells contained high amounts of F420 (0.6 nmol/mg protein). In extracts of starch-grown cells, the following enzymes of a modified Embden-Meyerhof pathway were detected: ADP-dependent hexokinase (ADP-HK), phosphoglucose isomerase, ADP-dependent 6-phosphofructokinase (ADP-PFK), fructose-1,6-phosphate aldolase, glyceraldehyde-3-phosphate:ferredoxin oxidoreductase (GAP:FdOR), phosphoglycerate mutase, enolase, and pyruvate kinase (PK). Specific activities of ADP-HK, ADP-PFK, GAP:FdOR, and PK were significantly higher in starch-grown cells than in lactate-grown cells, indicating induction of these enzymes during starch catabolism. Pyruvate conversion to acetate involved pyruvate:ferredoxin oxidoreductase and ADP-forming acetyl-CoA synthetase. The findings indicate that the archaeal sulfate reducer A. fulgidus strain 7324 converts starch to acetate via a modified Embden-Meyerhof pathway and acetyl-CoA synthetase (ADP-forming). This is the first report of growth of a sulfate reducer on starch, i.e. on a polymeric sugar.
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PMID:Sugar utilization in the hyperthermophilic, sulfate-reducing archaeon Archaeoglobus fulgidus strain 7324: starch degradation to acetate and CO2 via a modified Embden-Meyerhof pathway and acetyl-CoA synthetase (ADP-forming). 1170 74

The purpose of this study was to characterize the retention kinetics of recombinant human bone morphogenetic protein-2 (rhBMP-2) applied to two calcium-based delivery matrices. Biphasic calcium phosphate (BCP) and a composite containing BCP in an absorbable collagen sponge (BCP/ACS) were evaluated using a spinal fusion model in rabbits. rhBMP-2 labeled with radioactive iodine (125I) was used as a tracer to assess in vivo retention of rhBMP-2 in the presence of these materials (nine animals per material studied). Over a 36 day study period, animals were assessed for the following: percent administered dose retained at the implant site as measured by scintigraphic imaging (counting) with a gamma camera (all animals), radiography of the implant site (all animals), radioactivity in blood and plasma (all animals), and radioactivity in the urine and feces (three animals for each material). Radioactivity data were corrected for the decay of 125I and the attenuation between the implant in vivo and the gamma camera. Differences observed between the two materials for the area under the retention vs. time profile (AUC; 988%*day for BCP vs. 1070%*day for BCP/ACS, p = 0.57) and the mean residence time (MRT; 10.2 days for BCP vs. 7.6 days for BCP/ACS, p = 0.06) were not statistically significant. Initial retention/incorporation of rhBMP-2 was slightly higher for rhBMP-2/BCP/ACS than for rhBMP-2/BCP (96.8% vs. 86.0%, p < 0.05). Animals receiving rhBMP-2/BCP showed a longer terminal retention half-life (t1/2) than did those receiving rhBMP-2/BCP/ACS (7.5 vs. 4.5 days, p < 0.05). The urinary radioactivity recovery data supported the data obtained by scintigraphy. Over the 36 day collection period, essentially complete recovery of radioactivity (dose) in urine was observed for rhBMP-2/BCP and rhBMP-2/BCP/ACS and the majority of the radioactivity (approximately 95%) was soluble in trichloroacetic acid, suggesting extensive catabolism of rhBMP-2 before renal excretion. Fecal recovery of radioactivity was low, approximately 2-3%. In conclusion, rhBMP-2 was retained at the implant site when delivered with either BCP or BCP/ACS based on mean residence time and area under the retention curve vs. time profile. Use of these matrices resulted in detectable rhBMP-2 levels at the surgical site for over a week in contrast to data reported with several other matrices that lasted less time. Systemic catabolism and elimination of the rhBMP-2 was extensive and systemic presence of the protein was negligible.
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PMID:Retention of 125I-labeled recombinant human bone morphogenetic protein-2 by biphasic calcium phosphate or a composite sponge in a rabbit posterolateral spine arthrodesis model. 1238 73

Hyperthermophiles are a group of microorganisms that have their optimum growth temperature above 80 degrees C. More than 60 species of the hyperthermophiles have been isolated from marine and continental volcanic environments. Most hyperthermophiles belong to Archaea, the third domain of life, and are considered to be the most ancient of all extant life forms. Recent studies have revealed the presence of unusual sugar metabolic processes in hyperthermophilic archaea, for example, a modified Embden-Meyerhof pathway, that has so far not been observed in bacteria and eucarya. Several novel enzymes, such as ADP-dependent glucokinase, ADP-dependent phosphofructokinase, glyceraldehyde-3-phosphate ferredoxin oxidoreductase, phosphoenolpyruvate synthase, pyruvate : ferredoxin oxidoreductase, and ADP-forming acetyl-CoA synthetase, have been found to be involved in a modified Embden-Meyerhof pathway of the hyperthermophilic archaeon Pyrococcus furiosus. In addition, a unique mode of ATP regeneration has been postulated to exist in the pathway of P. furiosus. The metabolic design observed in this microorganism might reflect the situation at an early stage of evolution.
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PMID:Unique sugar metabolism and novel enzymes of hyperthermophilic archaea. 1476 28


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