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 synthase (EC 6.2.1.1), Propionyl-CoA synthase (EC 6.2.1.-) and butyryl-CoA synthase (EC 6.2.1.2) were measured in subcellular fractions prepared by primary and density-gradient fractionation from adult rat brain by a method resulting in recoveries close to 100%. Most of the activity of the three enzymes was recovered in the crude mitochondrial fraction. On subfractionation of this crude mitochondrial fraction with continuous sucrose density gradients, most of the activity of the three enzymes was found at a higher density than NAD+-isocitrate dehydrogenase and at about the same density as glutamate dehydrogenase, confirming earlier reported data for acetyl-CoA synthase. The finding that propionyl-CoA synthase and butyryl-CoA synthase had about the same distribution in the gradients as acetyl-CoA synthase adds support to the hypothesis that mitochondria involved in the metabolism of these short-chain fatty acids (all three of which have been shown to result in a rapid and high labelling of glutamine in vivo) form a distinct subpopulation of the total mitochondrial population. The three synthase activities were found to differ from each other in their rate of change and their subcellular localization during rat brain development. This, in combination with the observation that in gradients of adult brain preparations the three activities did not completely overlap, suggests that the three synthase activities are not present in the same proportion to each other in the same subpopulation (s) of mitochondria in the brain.
Biochem J 1975 Dec
PMID:Short-chain fatty acid synthesis in brain. Subcellular localization and changes during development. 0 95

The acetate activating system of Acetobacter aceti has been studied. The enzyme responsible, acetyl-CoA synthetase, has been purified about 500-fold from crude cell extracts and was approximately 85% pure as judged by polyacrylamide gel electrophoresis in sodium dodecyl sulphate. The purified enzyme showed optimal activity at pH 7.6 in both Tris-HCL and potassium phosphate buffers. In its purest form, the enzyme was stable at 4 degrees-C but denatured upon freezing. The Km values for CoA, ATP and acetate were found to be 0.104 mM, 0.36 mM and 0.25 mM respectively; propionate and acrylate were also activated by the enzyme but not butyrate, isobutyrate or valerate. GTP, UTP, CTP and ADP could not replace ATP in the reaction, and cysteine or pantetheine failed to replace CoA. The cationic requirements were studied and of the divalent cations tested, only Mn2+ could significantly replace Mg2+ in the reaction; K+ and NH4+ stimulated enzyme activity but inhibited at high concentrations; Na+ was a poor activator, but did not inhibit at higher concentrations. The effect of a number of glucose and other metabolites on enzyme activity has been tested.
Biochim Biophys Acta 1976 Dec 20
PMID:Characterization of the acetyl-CoA synthetase of Acetobacter aceti. 1

Thirteen chromosomal loci have been identified which affect acetate metabolism in Coprinus. Mutants at only two loci, acu-l and acu-7, are deficient in isocitrate lyase (ICL) (EC 4.1.3.1) activity. acu-1 mutants are unable to induce ICL because they lack acetyl-CoA synthetase which is required to convert acetate to the metabolic inducer of ICL. acu-7 is the structural gene for ICL. This was shown by selecting temperature sensitive acu+ revertants resulting from a second mutation within the acu-7 gene. One such revertant was shown to produce an ICL protein which was more thermolabile than the wild type enzyme. Other workers have postulated that ICL activity is important during asexual morphogenesis in fungi. No evidence was found for this in Coprinus. The morphological mutant oidial, which produces abundant asexual spores even in submerged culture, had the same low uninduced level of ICL activity as the wild type. Moreover, an acu-7 mutation had no effect on the expression of the oidial phenotype.
Mol Gen Genet 1977 Dec 09
PMID:Genetics and function of isocitrate lyase in Coprinus. 60 Feb 68

To evaluate the quantitative relationships between resting potassium-43 (43K) myocardial imaging and left ventricular segmental contraction abnormalities, 15 patients were studied by both radionuclide and contrast angiographic techniques at least two months following transmural myocardial infarction. The ECG location of infarction involved the anterior wall alone in six patients, inferior wall alone in three patients, both anterior and inferior walls in five patients, and in one patient ECG-anatomic correlation was obscured by newly developed left bundle branch block. 43K defects were noted in all patients. Anterior wall 43K defects were noted in all patients with previous anterior infarction and seven of nine inferior infarcts. These 43K defects were associated with a quantifiable decrease in regional radioactivity of at least 20% of normal appearing zones, and their location correlated with the angiographic site of akinesis or dyskinesis. The extent of the 43K defect (% 43K HP [% potassium 43 hypoperfusion]) was measured by planimetry and averaged 49% of the anterior view image (range 25-66%), 43% of the left anterior oblique image (range 0-58%), with the mean of both views being 47% (range 17-62%). The mean total area of the anterior image was 58 cm2 (range 40-101 cm2). The extent of the 43K defect (% 43K HP) was related to the extent of segmental contraction abnormality (% ACS). Correlations between % ACS and anterior view % 43K HP (r = 0.67), left anterior oblique % 43K HP (r = 0.54), and mean % 43K HP (r = 0.77) were found. The total size of the anterior view image correlated with left ventricular end-diastolic volume (r = 0.79). Thus, in this initial group of patients following transmural infarction, potassium-43 imaging can be accurately and quantitatively correlated with the site and extent of regional ventricular dysfunction as it is assessed by quantitative left ventricular angiography.
Circulation 1975 Dec
PMID:Quantitative relationships between potassium-43 imaging and left ventricular cineangiography following myocardial infarction in man. 118 52

1. Homogenates of rat epididymal fat pad, heart, kidney, lactating mammary gland, liver, skeletal muscle and small intestinal mucosa have been partitioned into a particulate and supernatant fraction. With reliable marker enzymes for the mitochondrial matrix and the cytosol: propionyl-CoA carboxylase and pyruvate kinase, the distributions of the acyl-CoA synthetase activities measured at 1 and 10 mM C2, C3 and C4 over mitochondria and cytosol have been calculated. From these values an estimate was made of the K0.5 of the fatty acids. 2. A distinct fatty acid-activating enzyme was assumed to be present in one of the compartments when that fatty acid was activated with a K0.5 less than or equal to 1.5 mM in an amount of greater than 13% of the total cellular activity. Adipose tissue, gut, liver and mammary gland, all organs of a high lipogenetic capacity, contained a cytosolic acetyl-CoA synthetase. At 1 mM acetate 60, 31, 77 and 83% of the total cellular activities in these organs were cytosolic in nature, with activities of 0.021, 0.32, 0.37 and 1.16 mumol C2 activated per min per g wet weight, respectively. 3. Mitochondrial acetyl-CoA and butyryl-CoA synthetases were found in adipose tissue, gut, heart, kidney, mammary gland and muscle. They were absent in liver. Adipose tissue and liver contained a mitochondrial propionyl-CoA synthetase with activities at 1 mM C3 of 0.014 and 1.50 mumol C3 activated per min per g wet weight, respectively. 4. At 1 mM, C2 was activated with decreasing rates by kidney, heart, mammary gland and gut (7.6-1.0 mumol C2 activated per min per g wet weight). C3 (1 mM) activation was about equal (1.6-1.9 mumol C3 activated per min per g wet weight) in liver, kidney and heart. C4 (1 mM) was activated with decreasing rates by heart, liver, kidney and gut (4.0-0.5 mumol C4 activated per min per g wet weight) in the order given. 5. The influence of the isolation method and the diet on fatty acid activation in small intestinal mucosal scrapings have been studied. To demonstrate the existence of cytosolic acetyl-CoA synthetase in fed animals a pre-treatment of everted intestine by low amplitude vibration has been found essential. Also C16 activation was highly (95%) decreased in a non-pre-vibrated preparation. 24 h starvation lowered cytosolic C2 and total C16 activation by 90 and 80%, respectively. Refeeding of starved rats with a balanced fat-free diet, and not with sucrose only, gave the same cytosolic C2 and total C16 activation as normally fed rats. 6. In guienea-pig heart, kidney, liver and muscle about the same partitions have been found as in the respective rat organs. The acetate activation in liver was factor 6 lower. Acetate and butyrate activation in guinea-pig muscle was much higher (6 and 37 times, respectively).
Biochim Biophys Acta 1975 Dec 17
PMID:Organ and intracellular localization of short-chain acyl-CoA synthetases in rat and guinea-pig. 120 46

Sixty-two mutants of the filamentous fungus Neurospora crassa were isolated on the basis of resistance to the antimetabolite fluoroacetate. Of these, 14 were unable to use acetate as sole carbon source (acetate non-utilizers, acu) and were the subject of further genetic and biochemical analysis. These mutants fell into four complementation groups, three of which did not complement any known acu mutants. Mutants of complementation group 3 failed to complement acu-8, demonstrated similar phenotypic properties and proved to be closely linked (less than 2% recombination) but not allelic. Representatives of groups 2 and 4 were mapped to independent loci; the single representative of group 1 could not be mapped. The four complementation groups were therefore designated as genes acu-10 to acu-13 respectively. All the mutants demonstrated normal acetate-induced expression of acetyl-CoA synthetase and the unique enzymes of the glyoxylate cycle and gluconeogenesis. The nature of these mutations is therefore quite different to those reported for other fungal species. Mutant acu-11 was unable to fix labelled acetate, indicating the loss of an initial transport function; partial enzyme lesions were observed for acu-12 (acetyl-CoA hydrolase) and acu-13 (acetate-inducible NAD(+)-specific malate dehydrogenase).
J Gen Microbiol 1992 Dec
PMID:Isolation and characterization of new fluoroacetate resistant/acetate non-utilizing mutants of Neurospora crassa. 136 82

A DNA fragment of Saccharomyces cerevisiae with high homology to the acetyl-coenzyme A (acetyl-CoA) synthetase genes of Aspergillus nidulans and Neurospora crassa has been cloned, sequenced and mapped to chromosome I. It contains an open reading frame of 2139 nucleotides, encoding a predicted gene product of 79.2 kDa. In contrast to its ascomycete homologs, there are no introns in the coding sequence. The first ATG codon of the open reading frame is in an unusual context for a translational start site, while the next ATG, 24 codons downstream, is in a more conventional context. Possible implications of two alternative translational start sites for the cellular localization of the enzyme are discussed. A stable mutant of this gene, obtained by the gene disruption technique, had the same low basal activity of acetyl-CoA synthetase as wild-type cells when grown on glucose but completely lacked the strong increase in activity upon entering the stationary phase, providing direct proof that the gene encodes an inducible acetyl-CoA synthetase (ACS1) of yeast. As expected, the mutant was unable to grow on acetate as sole carbon source. Nevertheless, it showed normal induction of isocitrate lyase on acetate media, indicating that activity of acetyl-CoA synthetase is dispensable for induction of the glyoxylate cycle in S. cerevisiae. Surprisingly, disruption of the ACS1 gene did not affect growth on media containing ethanol as the sole carbon source, demonstrating that there are alternative pathways leading to acetyl-CoA under these conditions.
Yeast 1992 Dec
PMID:Cloning and disruption of a gene required for growth on acetate but not on ethanol: the acetyl-coenzyme A synthetase gene of Saccharomyces cerevisiae. 136 52

Overall, there is a wide range of programs offered at the community level. Most of the group cessation clinics, both nonprofit and commercial, typically offer group support, behavior modification, and stress and weight management, with similar emphases in their companion self-help manuals. It often is difficult to distinguish between the various methods employed by the diverse programs, with those that offer maintenance and relapse prevention components faring the best. In general, the multiple-component programs, whether group or self-help packages, seem to hold the most promise for achieving and maintaining abstinence; however, there is some evidence that overwhelming the smoker with too many new behaviors and skills lowers the effectiveness of otherwise successful components. The challenges for community-based programs will be to modify and adapt their materials and sessions to address the needs uncovered in the recent emphasis on the process of smoking cessation. Specifically, program content must address the issue of recycling and relapse prevention. Smokers who have made unsuccessful quit attempts must be able to reframe those attempts in a positive manner, so that they are motivated to try again. Similarly, recent quitters need the skills and motivation to remain abstinent. Although some cessation programs allow clients to participate in future sessions or meetings for little or no extra cost, few have any strategies for dealing with long-term maintenance. As community-based programs incorporate these elements of cessation, quit rates are likely to increase. An additional challenge is found in the difficulty of reaching the hard-core, heavy smoker. There is little doubt that light-to-moderate smokers find it easier to achieve long-term cessation. Cessation programs that motivate heavy smokers to attempt to quit or that include adjunct therapies to assist the heavy smoker (i.e., nicotine gum) to quit smoking are likely to be positively received. Currently, however, efforts specifically designed to assist heavy smokers are experimental. A final challenge is to adapt materials and sessions to motivate and assist the hard-to-reach smokers. Increasingly, smoking is becoming a habit of individuals in lower socioeconomic groups, including minorities, non-high school graduates, and young women. Avenues that have been used to reach white middle-class Americans are not easily transferred to such groups. Some attention is already being paid to development of more culturally appropriate materials (e.g., the ALA Manual oriented to blue collar workers and the ACS focus on pregnant women); however, it remains a challenge to motivate members of these groups to participate in smoking cessation activities.(ABSTRACT TRUNCATED AT 400 WORDS)
Clin Chest Med 1991 Dec
PMID:Community-based programs for smoking cessation. 174 95

CO dehydrogenase/acetyl-coenzyme A synthase (CODH) is the central enzyme in the pathway of acetyl-coenzyme A biosynthesis in Clostridium thermoaceticum. It catalyzes the interconversion of CO and CO2 and the synthesis of acetyl-coenzyme A from the methylated corrinoid/iron sulfur protein, CO, and coenzyme A. It is a nickel-iron-sulfur protein and contains two subunits in the form (alpha beta)3. Reported here is the cloning and sequencing of the genes for both subunits of CODH. The gene for the alpha subunit codes for a protein with 729 amino acids and a molecular weight of 81,730, and the beta gene for a protein with 674 amino acids and a molecular weight of 72,928. The alpha subunit follows the beta subunit by 23 bases and the genes for both subunits are preceded by a sequence which is similar to the Shine-Dalgarno sequence of Escherichia coli. No significant amino acid sequence homology has been found to any known sequence. Labeling CODH with 2,4-dinitrophenylsulfenyl chloride and isolating labeled peptide fragments demonstrated that a tryptophan, residue 418 of the alpha subunit, is protected by coenzyme A and thus may be considered a potential part of the coenzyme A site.
J Biol Chem 1991 Dec 15
PMID:The primary structure of the subunits of carbon monoxide dehydrogenase/acetyl-CoA synthase from Clostridium thermoaceticum. 174 56

The authors examined a 2-month-old infant with clinical signs of Pfeiffer's syndrome (craniosynostosis, abnormalities of the extremities, normal psychomotor development). In the family other affected cases were revealed with a variable expressivity of the clinical signs. The authors draw attention to the importance of a detailed clinical, X-ray and anthropometric examination of different members of the family to detect carriership of the gene for ACS.
Cesk Pediatr 1989 Dec
PMID:[Pfeiffer's syndrome]. 263 58


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