6.2.1.1	evolution	the metalloprotein acetyl-coenzyme A synthase/carbon monoxide dehydrogenase, ACS/CODH, is a bifunctional metalloenzyme found in anaerobic archaea and bacteria that grow hemoautotrophically on CO or CO2, and is significant for biological carbon fixation and understanding the origin of life	714724	
6.2.1.1	malfunction	cyclic AMP inhibits the activity and promotes the acetylation of acetyl-CoA synthetase through competitive binding to the ATP/AMP pocket. cAMP directly binds to the enzyme and inhibits its activity in a substrate-competitive manner. cAMP binding increases SeAcs acetylation by simultaneously promoting Pat-dependent acetylation and inhibiting CobB-dependent deacetylation, resulting in enhanced SeAcs inhibition	-, 745369	
6.2.1.1	malfunction	decreased isoform ACSS2 expression inhibits renal cell carcinoma cell migration and invasion	744665	
6.2.1.1	malfunction	deletion of individual and multiple subunits of acetyl-CoA synthetase decreases CoA release activity for several different CoA ester substrates. Deletion of acetyl-CoA synthetases I and II increases production of 3-hydroxypropionate by the metabolically-engineered hyperthermophile Pyrococcus furiosus (containing three enzymes from the CO2 fixation cycle of the thermoacidophilic archaeon Metallosphaerasedula)	725872	
6.2.1.1	malfunction	growth on 10 mM acetate causes an acs+ induction in a Salmonella enterica strain, that cannot acetylate, i.e. inactivate Acs, leads to growth arrest, a condition that correlates with a drop in energy charge in the acetylation-deficient strain, relative to the energy charge in the acetylation-proficient strain. Acs-dependent depletion of ATP, coupled with the rise in AMP levels, prevents the synthesis of ADP needed to replenish the pool of ATP	716267	
6.2.1.1	malfunction	in adult mice, attenuation of hippocampal isoform ACSS2 expression impairs long-term spatial memory	745887	
6.2.1.1	metabolism	acetyl-CoA synthase, a subunit of the bifunctional CO dehydrogenase/acetyl-CoA synthase, CODH/ACS, complex of Moorella thermoacetica requires reductive activation in order to catalyze acetyl-CoA synthesis and related partial reactions, including the CO/acetyl-CoA exchange reaction. Ferredoxin(II), which harbors two [4Fe-4S] clusters and is an electron acceptor for CODH, serves as a redox activator of ACS. Ferredoxin interfaces with an internal redox shuttle in acetyl-CoA synthase during reductive activation and catalysis. The midpoint reduction potential for the catalytic one-electron redoxactive species in the CO/acetyl-CoAexchange reaction is -511 mV. Incubation of ACS with Fd-II and CO leads to the formation of the NiFeC species. Mechanism, overview	714240	
6.2.1.1	metabolism	activation of weak organic acids by acyl-CoA synthetases is costly to cells, since it requires 2 mol of ATP per mol of substrate; 1 mol of ATP is consumed to activate the organic acid, while the second mol of ATP is needed to convert AMP to ADP, the immediate precursor of ATP. Further loss of energy resources during the course of the Acs reaction is caused by the hydrolysis of diphosphate to monophosphate through pyrophosphate phosphohydrolase, EC 3.6.1.1	716267	
6.2.1.1	metabolism	isoform ACSS2 retains acetate to maintain histone acetylation	744656	
6.2.1.1	additional information	growth arrest is caused by elevated Acs activity, while overproduction of ADP-forming Ac-CoA synthesizing systems, EC 6.2.1.13, do not affect the growth behaviour of acetylation-deficient or acetylation-proficient strains, effects of Acs on growth of different strains, also sirtuin-dependent protein acylation/deacylation system-defective strains, overview. Increased CoA biosynthesis partially alleviates the negative effect caused by high Acs activity, regulation, overview	716267	
6.2.1.1	physiological function	acetyl-CoA synthetase 2 is a regulator of autophagy and lifespan	744651	
6.2.1.1	physiological function	acetyl-coenzyme A synthetase activates acetate into acetyl-coenzyme A in most cells. Salmonella enterica requires Acs activity for growth on acetate. The sirtuin-dependent protein acylation/deacylation system, SDPADS, controls the activity of Acs	716267	
6.2.1.1	physiological function	activation of acetate in energy metabolism	-, 726837	
6.2.1.1	physiological function	an acs2 deletion strain has a reduced replicative life span compared to wild-type and isoform acs1 deletion strains. Replicatively aged acs2 deletion cells contain elevated levels of extrachromosomal rDNA circles, and silencing at the rDNA locus is impaired in an acs2 deletion strain	705678	
6.2.1.1	physiological function	enzyme overexpression results in higher resistance to acetic acid as measured by an increased growth rate and shorter lag phase relative to a wild type strain, suggesting that enzyme-mediated consumption of acetic acid during fermentation contributes to acetic acid detoxification	744932	
6.2.1.1	physiological function	enzyme-mediated acetyl-CoA synthesis from acetate is necessary for human cytomegalovirus infection and can compensate for the loss of ATP-citrate lyase	746321	
6.2.1.1	physiological function	isoform ACSS2 is an important factor for promoting renal cell carcinoma development and is essential for cell migration and invasion	744665	
6.2.1.1	physiological function	the enzyme regulates histone acetylation and hippocampal memory	745887	
6.2.1.1	physiological function	the high-affinity biosynthetic pathway for converting acetate to acetyl-coenzyme A (acetyl-CoA) is catalyzed by the central metabolic enzyme acetyl-coenzyme A synthetase (Acs), which is finely regulated both at the transcriptional level via cyclic AMP (cAMP)-driven trans-activation and at the post-translational level via acetylation inhibition. The cAMP contact residues are well conserved from prokaryotes to eukaryotes, suggesting a general regulatory mechanism of cAMP on Acs. cAMP generally inhibits other acyl- or aryl-CoA synthetases	-, 745369	
6.2.1.1	physiological function	tumor cells express higher levels of cytosolic acetyl-CoA synthetase ACSS2 under hypoxia than normoxia. Knockdown of ACSS2 by RNA interference in tumor cells enhances tumor cell death under long-term hypoxia in vitro. The ACSS2 suppression slows tumor growth in vivo. Tumor cells excrete acetate and the quantity increases under hypoxia, the pattern of acetate excretion follows the expression pattern of ACSS2. The ACSS2 knockdown leads to a corresponding reduction in the acetate excretion in tumor cells	703038