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)

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

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.
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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

The ACS is a clinical entity that develops from progressive, acute increases in IAP and affects multiple organ systems in a graded fashion because of differential susceptibilities. The gut is the organ most sensitive to IAH, and it develops evidence of end-organ damage before the development of the classic renal, pulmonary, and cardiovascular signs. Intracranial derangements with ACS are now well described. Treatment involves expedient decompression of the abdomen, without which the syndrome of end-organ damage and reduced oxygen delivery may lead to the development of multiple organ failure and, ultimately, death. Multiple trauma, massive hemorrhage, or protracted operation with massive volume resuscitation are the situations in which the ACS is most frequently encountered. Knowledge of the ACS, however, is also essential for the management of critically ill pediatric patients (especially those with AWD) and in understanding the limitations of laparoscopy. The role of IAH in the pathogenesis of NEC, central obesity co-morbidities, and pre-eclampsia/eclampsia remains to be fully studied.
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PMID:Abdominal compartment syndrome. 975 58

Cells of Escherichia coli growing on sugars that result in catabolite repression or amino acids that feed into glycolysis undergo a metabolic switch associated with the production and utilization of acetate. As they divide exponentially, these cells excrete acetate via the phosphotransacetylase-acetate kinase pathway. As they begin the transition to stationary phase, they instead resorb acetate, activate it to acetyl coenzyme A (acetyl-CoA) by means of the enzyme acetyl-CoA synthetase (Acs) and utilize it to generate energy and biosynthetic components via the tricarboxylic acid cycle and the glyoxylate shunt, respectively. Here, we present evidence that this switch occurs primarily through the induction of acs and that the timing and magnitude of this induction depend, in part, on the direct action of the carbon regulator cyclic AMP receptor protein (CRP) and the oxygen regulator FNR. It also depends, probably indirectly, upon the glyoxylate shunt repressor IclR, its activator FadR, and many enzymes involved in acetate metabolism. On the basis of these results, we propose that cells induce acs, and thus their ability to assimilate acetate, in response to rising cyclic AMP levels, falling oxygen partial pressure, and the flux of carbon through acetate-associated pathways.
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PMID:Regulation of acetyl coenzyme A synthetase in Escherichia coli. 1089 24

Right handed healthy volunteers underwent functional magnetic resonance imaging (fMRI) examinations on a 1.5 Tesla MRI-scanner (Gyroscan ACS NT; Philips, Best, NL). Blood oxygen level dependent (BOLD) images were obtained using a three dimensional multi-shot echo planar imaging sequence employing a shifted echo technique (Principles of echo shifting with a train of observations). Finger tapping of the right hand was used as a task for motor stimulation. A total of 86 subjects was included into statistical analysis. Absolute and relative signal differences and cluster sizes of activation for the left motor cortex were obtained. In addition, Z-score, pooled Z-score and cross correlation activation maps were calculated and matched with high resolution anatomic images. A significant decrease with age could be detected for absolute and relative signal intensity differences for the whole group and for the male subgroup. Correlation analysis for the female subgroup also bore negative albeit non-significant correlation coefficients. An age-related decline of BOLD-contrast can be assumed to explain signal decrease. This age-related effect should be considered in clinical fMRI applications.
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PMID:Age related signal decrease in functional magnetic resonance imaging during motor stimulation in humans. 1147 8

Some yeasts, such as Saccharomyces cerevisiae, produce ethanol at fully aerobic conditions, whereas other yeasts, such as Kluyveromyces lactis, do not. In this study we investigated the occurrence of aerobic alcoholic fermentation in the petite-negative yeast Saccharomyces kluyveri that is only distantly related to S. cerevisiae. In aerobic glucose-limited continuous cultures of S. kluyveri, two growth regimens were observed: at dilution rates below 0.5 h(-1) the metabolism was purely respiratory, and at dilution rates above 0.5 h(-1) the metabolism was respiro-fermentative. The dilution rate at which the switch in metabolism occurred, i.e. the critical dilution rate, was 66% higher than the typical critical dilution rate of S. cerevisiae. The maximum specific oxygen consumption rate around the critical dilution rate was found to 13.6 mmol (g dry weight)(-1) h(-1) and the capacity of the pyruvate dehydrogenase-bypass pathway was estimated to be high from in vitro enzyme activities; especially the specific activity of acetyl-CoA synthetase was much higher than in S. cerevisiae at all tested conditions. Addition of glucose to respiring cells of S. kluyveri led to ethanol formation after a delay of 20-50 min (depending on culture conditions prior to the pulse), which is in contrast to S. cerevisiae that ferments immediately after glucose addition.
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PMID:Steady-state and transient-state analyses of aerobic fermentation in Saccharomyces kluyveri. 1270 11

We reported that melatonin prevents the progression of carbon tetrachloride (CCl4)-induced acute liver injury in rats possibly by attenuating enhanced lipid peroxidation and reduced glutathione depletion. Herein, we examined the effect of melatonin on the changes in hepatic reactive oxygen species (ROS) metabolism in rats with a single intraperitoneal injection of CCl4 (1.6 g/kg body weight); the intent was to clarify the therapeutic mechanism of the indoleamine on CCl4-induced acute liver injury. Rats with and without CCl4 treatment received a single oral dose of melatonin (10, 50 or 100 mg/kg body weight) 6 hr after CCl4 treatment. Hepatic concentrations of ascorbic acid (ASC) and vitamin E (VE) and hepatic activities of superoxide dismutase (SOD), catalase (CAT), Se-glutathione peroxidase (Se-GSH-Px), glutathione reductase (GSSG-R), glucose-6-phosphate dehydrogenase (G-6-PDH), and xanthine oxidase (XO) were determined 6 and 24 hr after CCl4 treatment. The liver of CCl4-treated rats showed reductions in ASC concentrations, and SOD activity and an increase in G-6-PDH activity at 6 hr after treatment and further decreases in ACS concentrations and SOD activity and also further increase in G-6-PDH activity in addition to decreases in CAT and GSSG-R activities and increases in VE concentrations and XO activity at 24 hr after treatment. Melatonin attenuated the reductions in hepatic ASC concentrations and SOD, CAT and GSSG-R activities and the increase in hepatic XO activity in a dose-dependent manner without affecting either hepatic Se-GSH-Px activity or the increased hepatic VE concentration and G-6-PDH activity at 24 hr after CCl4 treatment. No dose of melatonin influenced hepatic ACS and VE concentrations and SOD, CAT, Se-GSH-Px, G-6-PDH, and XO activities in CCl4-untreated rats. These results indicate that melatonin postadministered at pharmacological doses prevents the disruption of hepatic ROS metabolism associated with ASC, SOD, CAT, GSSG-R, and XO, in addition to reduced glutathione, in CCl4-treated rats.
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PMID:Melatonin prevents disruption of hepatic reactive oxygen species metabolism in rats treated with carbon tetrachloride. 1467 25

Data from laboratory-scale sequencing batch reactors operated in an anaerobic-aerobic cycle showed that a low influent phosphorus/chemical oxygen demand (COD) ratio feed favored a glycogen-accumulating metabolism (GAM)-dominated culture and that a high influent phosphorus/COD ratio feed favored a polyphosphate-accumulating metabolism (PAM)-dominated culture. The PAM-dominated culture anaerobically took up acetate approximately 7 times faster than the GAM-dominated culture. Adenosine triphosphate (ATP) balances were performed assuming eight different metabolic scenarios that included the Entner-Doudoroff or the Embden-Myerhof glycolytic pathway, acetyl-coenzyme A (CoA) synthase or the acetate kinase-phospho-transacetylase (AK-PTA) system for acetyl-CoA synthesis, and ATP synthesis or no ATP synthesis during fumarate reduction. The ATP available for transport of acetate into the cell (2) was calculated using these balances. The assumed quantity of ATP produced during fumarate reduction had a relatively small effect on alpha, particularly when PAM was dominant. When GAM was dominant, little or no ATP was available for acetate transport depending on the assumed scenario, and the Embden-Myerhof pathway was more feasible. The value of alpha increased with increasing PAM dominance for all eight metabolic pathways. The maximum calculated alpha value of 0.5 mol ATP/C-mol acetate uptake occurred at maximum PAM dominance and when the Embden-Myerhof pathway was active, when ATP was produced during fumarate reduction, and when the AK-PTA system was active. This value of alpha was higher than previously calculated values with the same metabolic assumptions. An acetate uptake mechanism was suggested that included acetyl-CoA synthetase and direct regeneration of the proton motive force by a proton-translocating pyrophosphatase. Polyphosphate-accumulating metabolism may have a competitive advantage over GAM through a higher anaerobic acetate uptake rate made possible by a greater use of energy for acetate uptake, by use of a different acetate uptake mechanism, or both.
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PMID:Enhanced biological phosphorus removal from wastewater by biomass with different phosphorus contents, Part II: Anaerobic adenosine triphosphate utilization and acetate uptake rates. 1470 9

Hemoproteins carry out diverse functions utilizing a wide range of chemical reactivity while employing the same heme prosthetic group. It is clear from high-resolution crystal structures and biochemical studies that protein-bound hemes are not planar and adopt diverse conformations. The crystal structure of an H-NOX domain from Thermoanaerobacter tengcongensis (Tt H-NOX) contains the most distorted heme reported to date. In this study, Tt H-NOX was engineered to adopt a flatter heme by mutating proline 115, a conserved residue in the H-NOX family, to alanine. Decreasing heme distortion in Tt H-NOX increases affinity for oxygen and decreases the reduction potential of the heme iron. Additionally, flattening the heme is associated with significant shifts in the N-terminus of the protein. These results show a clear link between the heme conformation and Tt H-NOX structure and demonstrate that heme distortion is an important determinant for maintaining biochemical properties in H-NOX proteins.
ACS Chem Biol 2008 Nov 21
PMID:Probing the function of heme distortion in the H-NOX family. 1903 89

Acetate is activated to acetyl-CoA by acetyl-CoA synthetase 2 (AceCS2), a mitochondrial enzyme. Here, we report that the activation of acetate by AceCS2 has a specific and unique role in thermogenesis during fasting. In the skeletal muscle of fasted AceCS2(-/-) mice, ATP levels were reduced by 50% compared to AceCS2(+/+) mice. Fasted AceCS2(-/-) mice were significantly hypothermic and had reduced exercise capacity. Furthermore, when fed a low-carbohydrate diet, 4-week-old weaned AceCS2(-/-) mice also exhibited hypothermia accompanied by sustained hypoglycemia that led to a 50% mortality. Therefore, AceCS2 plays a significant role in acetate oxidation needed to generate ATP and heat. Furthermore, AceCS2(-/-) mice exhibited increased oxygen consumption and reduced weight gain on a low-carbohydrate diet. Our findings demonstrate that activation of acetate by AceCS2 plays a pivotal role in thermogenesis, especially under low-glucose or ketogenic conditions, and is crucially required for survival.
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PMID:Fasting-induced hypothermia and reduced energy production in mice lacking acetyl-CoA synthetase 2. 1918 75


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