Information on EC 6.2.1.1 - acetate-CoA ligase

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The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea

EC NUMBER
COMMENTARY hide
6.2.1.1
-
RECOMMENDED NAME
GeneOntology No.
acetate-CoA ligase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
ATP + acetate + CoA = AMP + diphosphate + acetyl-CoA
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Acid-thiol ligation
-
-
-
-
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
acetate conversion to acetyl-CoA
-
-
adlupulone and adhumulone biosynthesis
-
-
chitin degradation to ethanol
-
-
cis-genanyl-CoA degradation
-
-
colupulone and cohumulone biosynthesis
-
-
ethanol degradation II
-
-
ethanol degradation III
-
-
ethanol degradation IV
-
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L-isoleucine biosynthesis V
-
-
lupulone and humulone biosynthesis
-
-
acetate fermentation
-
-
propanol degradation
-
-
Glycolysis / Gluconeogenesis
-
-
Pyruvate metabolism
-
-
Propanoate metabolism
-
-
Methane metabolism
-
-
Carbon fixation pathways in prokaryotes
-
-
Metabolic pathways
-
-
Biosynthesis of secondary metabolites
-
-
Microbial metabolism in diverse environments
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-
Biosynthesis of antibiotics
-
-
SYSTEMATIC NAME
IUBMB Comments
acetate:CoA ligase (AMP-forming)
Also acts on propanoate and propenoate.
CAS REGISTRY NUMBER
COMMENTARY hide
9012-31-1
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
strain ATCC 8554
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-
Manually annotated by BRENDA team
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-
-
Manually annotated by BRENDA team
gene acs
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-
Manually annotated by BRENDA team
gene acs
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-
Manually annotated by BRENDA team
Amaranthus sp.
-
-
-
Manually annotated by BRENDA team
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-
-
Manually annotated by BRENDA team
gene acsA
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-
Manually annotated by BRENDA team
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-
-
Manually annotated by BRENDA team
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-
-
Manually annotated by BRENDA team
; DSM 18386
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-
Manually annotated by BRENDA team
DSM 18386
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-
Manually annotated by BRENDA team
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-
-
Manually annotated by BRENDA team
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-
-
Manually annotated by BRENDA team
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-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
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Uniprot
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
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-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
Taxus sp.
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
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
malfunction
metabolism
physiological function
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
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
ADP + acetate + CoA
AMP + diphosphate + acetyl-CoA
show the reaction diagram
ADP + phosphate + acetyl-CoA
ATP + acetate + CoA
show the reaction diagram
-
-
-
-
?
ATP + 3-bromopropanoate + CoA
AMP + diphosphate + 3-bromopropanoyl-CoA
show the reaction diagram
-
-
-
-
-
ATP + 3-chloropropanoate + CoA
AMP + diphosphate + 3-chloropropanoyl-CoA
show the reaction diagram
-
-
-
-
-
ATP + 3-methylvalerate + CoA
AMP + diphosphate + 3-methylvaleryl-CoA
show the reaction diagram
-
mutant enzyme W416G catalyzes the reaction, no activity with wild-type enzyme
-
-
?
ATP + 4-methylvalerate + CoA
AMP + diphosphate + 4-methylvaleryl-CoA
show the reaction diagram
-
mutant enzyme W416G catalyzes the reaction, no activity with wild-type enzyme
-
-
?
ATP + acetate + CoA
?
show the reaction diagram
ATP + acetate + CoA
AMP + diphosphate + acetyl-CoA
show the reaction diagram
ATP + acetate + seleno-CoA
AMP + diphosphate + acetyl-seleno-CoA
show the reaction diagram
-
-
-
-
-
ATP + acrylate + CoA
AMP + diphosphate + acryloyl-CoA
show the reaction diagram
ATP + butyrate + CoA
AMP + diphosphate + butyryl-CoA
show the reaction diagram
ATP + fluoroacetate + CoA
AMP + diphosphate + fluoroacetyl-CoA
show the reaction diagram
ATP + formate + CoA
AMP + diphosphate + formyl-CoA
show the reaction diagram
-
27% of the activity with acetate
-
-
?
ATP + heptanoate + CoA
AMP + diphosphate + heptanoyl-CoA
show the reaction diagram
ATP + hexanoate + CoA
AMP + diphosphate + hexanoyl-CoA
show the reaction diagram
ATP + isobutyrate + CoA
AMP + diphosphate + isobutyryl-CoA
show the reaction diagram
-
28% of the activity with acetate
-
-
?
ATP + methacrylic acid + CoA
AMP + diphosphate + methacryloyl-CoA
show the reaction diagram
-
-
-
-
-
ATP + octanoate + CoA
AMP + diphosphate + octanoyl-CoA
show the reaction diagram
-
mutant enzyme W416G catalyzes the reaction, no activity with wild-type enzyme
-
-
?
ATP + pentanoate + CoA
AMP + diphosphate + pentanoyl-CoA
show the reaction diagram
-
6.7% of the activity relative to acetate
-
-
-
ATP + potassium acetate + CoA
AMP + acetyl-CoA + potassium diphosphate
show the reaction diagram
A0A144QFN1;
-
-
-
?
ATP + propanoate + CoA
AMP + diphosphate + propanoyl-CoA
show the reaction diagram
ATP + propionate + CoA
AMP + diphosphate + propionyl-CoA
show the reaction diagram
ATP + sodium acetate + CoA
AMP + acetyl-CoA + sodium diphosphate
show the reaction diagram
A0A144QFN1;
-
-
-
?
ATP + sodium acetate + CoA
AMP + diphosphate + sodium acetyl-CoA
show the reaction diagram
-
-
-
-
?
ATP + tetrapolyphosphate
adenosine 5'-pentaphosphate
show the reaction diagram
-
-
-
-
ATP + tripolyphosphate
adenosine 5'-tetraphosphate
show the reaction diagram
-
-
-
-
ATP + valerate + CoA
AMP + diphosphate + valeryl-CoA
show the reaction diagram
CheY + acetyl-CoA + ATP
acetyl-CheY + CoA + AMP + diphosphate
show the reaction diagram
-
CheY is the the excitatory response regulator in the chemotaxis system of Escherichia coli, acetyl-CoA synthetase-catalyzed transfer of acetyl groups from acetate to CheY and autocatalyzed transfer from AcCoA, mechanism, overview
-
-
?
CTP + acetate + CoA
CMP + diphosphate + acetyl-CoA
show the reaction diagram
-
-
-
-
-
dATP + acetate + CoA
dAMP + diphosphate + acetyl-CoA
show the reaction diagram
GTP + acetate + CoA
GMP + diphosphate + acetyl-CoA
show the reaction diagram
-
-
-
-
-
UTP + acetate + CoA
UMP + diphosphate + acetyl-CoA
show the reaction diagram
-
-
-
-
-
additional information
?
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
ATP + acetate + CoA
?
show the reaction diagram
ATP + acetate + CoA
AMP + diphosphate + acetyl-CoA
show the reaction diagram
ATP + propionate + CoA
AMP + diphosphate + propionyl-CoA
show the reaction diagram
CheY + acetyl-CoA + ATP
acetyl-CheY + CoA + AMP + diphosphate
show the reaction diagram
-
CheY is the the excitatory response regulator in the chemotaxis system of Escherichia coli, acetyl-CoA synthetase-catalyzed transfer of acetyl groups from acetate to CheY and autocatalyzed transfer from AcCoA, mechanism, overview
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-
?
dATP + acetate + CoA
dAMP + diphosphate + acetyl-CoA
show the reaction diagram
Q99NB1
AceCS2 plays a role in the production of energy under ketogenic conditions, such as starvation and diabetes. Acetyl-CoAs produced by AceCS2 are utilized mainly for oxidation
-
?
additional information
?
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Cd2+
-
two types of divalent metal ion requirement, 1. Mg2+, Mn2+, Fe2+, Co2+ or Ca2+ required for the formation of the enzyme-bound acetyl adenylate, 2. Ni2+, Cd2+, Fe2+ or Cu2+ required for adenylate binding
Cu2+
-
two types of divalent metal ion requirement, 1. Mg2+, Mn2+, Fe2+, Co2+ or Ca2+ required for the formation of the enzyme-bound acetyl adenylate, 2. Ni2+, Cd2+, Fe2+ or Cu2+ required for adenylate binding
KCl
-
optimal activity at 1-1.5 M
Li+
-
activation at 5-8 mM, absolute requirement for certain monovalent cations, inhibition above 10 mM
Ni
-
nickel-containing bimetallic site, the bifunctional enzyme carbon monoxide dehydrogenase/acetyl-coenzyme A synthase
Rb+
-
activates, absolute requirement for certain monovalent cations, no inhibition at high concentrations
Tris
-
activates, absolute requirement for certain monovalent cations, no inhibition at high concentrations
additional information
-
the enzyme uses seven metalloclusters in four reaction steps, overview
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(NH4)2SO4
3'-Dephospho-CoASH analogues with a phosphodiester bond
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-
-
5,5'-dithiobis(2-nitrobenzoate)
-
-
acetyl-CoA
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competitive to CoASH
adenylate
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-
ADP
-
competitive to ATP
Allicin
bicarbonate
-
-
Butyrate
-
propanoate-CoA formation
cAMP
-
cyclic AMP inhibits the activity and promotes the acetylation of acetyl-CoA synthetase through competitive binding to the highly conserved ATP/AMP binding pocket and restrains SeAcs in an open conformation. 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
CO
-
CO inhibits acetyl-CoA synthesis quite strongly and in a cooperative manner
Dicarbonic acid diethyl ester
-
-
diphosphate
erythrose 4-phosphate
-
-
glyceraldehyde 3-phosphate
-
weak
glycerol
glyoxylate
-
-
long-chain acyl-CoA compounds
Monovalent cations
-
at 200 mM
-
NaCl
-
concentration of 5-20 mM decrease the activity 20-25%
Ni
-
the authors favor a mechanism in which methylation occurs first to Ni(p0 -) or Ni(pI -)[Fe4S4]+, followed by coordination of CO to form Ni(pII)(CO)(CH3) which breaks one of the S(Nid) bonds (forming the bis square planar Ni(II) species, as if the Ni(d)N2S2 unit were acting as a biological pseudodiphosphine, mimicking behavior common to a bidentate phosphine). The CO-insertion/CH3-migration occurs on one metal forming the trigonal planar Ni(pII)-acetyl intermediate. Finally, addition of thiolate produces the thioester. The authors disfavor the unprecedented bimetallic, CO-insertion/CH3-migration mechanism (both in its diamagnetic and paramagnetic guise) and disfavors CO, CH3+, or thiolate (CoA) binding to the distal Ni. Finally, Ni in the proximal site produces a better catalyst than does Cu
Nonidet P40
-
weak
O2
-
the enzyme is O2-sensitive
p-chloromercuribenzoate
-
-
p-hydroxymercuribenzoate
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inhibition is reversible by either CoA or mercaptoethanol
P1,P5-di(adenosine-5)pentaphosphate
-
inhibits ADP formation
palmitoyl-CoA
propanoate
-
butyryl-CoA formation
pyridoxal 5'-phosphate
-
-
Seleno-CoA
-
competitive to CoA
Short-chain CoA esters
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-
-
sorbitol
Sucrose
Tween 100
-
-
-
Xylulose 5-phosphate
-
-
additional information
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
2-mercaptoethanol
-
stimulates
acetate
CobB Sir2 protein
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activation of the acetylated enzyme requires the nicotinamide adenine dinucleotide-dependent protein deacetylase activity of the CobB Sir2 protein
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DTT
-
stimulates
GSH
-
stimulates
reduced ferredoxin
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required
SIR2 protein
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short-chain fatty acid activation by acyl-coenzyme A synthetases requires SIR2 protein function
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SIRT1
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AceCS1 is completely inactivated upon acetylation and is rapidly reactivated by SIRT3 deacetylation
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SIRT3
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AceCS2 is completely inactivated upon acetylation and is rapidly reactivated by SIRT3 deacetylation
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
29.2
2-methylvalerate
-
65°C, mutant enzyme W416G
7.6
4-methylvalerate
-
65°C, mutant enzyme W416G
0.04 - 11000
acetate
0.0037 - 1.8
acetyl-CoA
5.26 - 17
Acrylate
0.093 - 0.4
ADP
0.017 - 17
ATP
0.46 - 151.9
Butyrate
0.011 - 1.2
CoA
31.2
fluoroacetate
-
-
10.2
Heptanoate
-
65°C, mutant enzyme W416G
6.1
hexanoate
-
65°C, mutant enzyme W416G
0.65 - 6.6
MgATP2-
18.1
Octanoate
-
65°C, mutant enzyme W416G
0.23 - 0.272
phosphate
3.59
potassium acetate
A0A144QFN1;
at pH 8.0 and 37°C
3.1 - 10.5
propanoate
3.9 - 188.8
propionate
0.25 - 4.66
Sodium acetate
4.7
tripolyphosphate
-
synthesis of adenosine 5´-tetraphosphate
11.1
valerate
-
65°C, mutant enzyme W416G
additional information
additional information
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.67
2-methylvalerate
-
65°C, mutant enzyme W416G
10.9
4-methylvalerate
-
65°C, mutant enzyme W416G
0.3 - 9400
acetate
0.3 - 100.6
ATP
0.013 - 10.8
Butyrate
0.3 - 144.9
CoA
7.3
Heptanoate
-
65°C, mutant enzyme W416G
5.9
hexanoate
-
65°C, mutant enzyme W416G
3.3
Octanoate
-
65°C, mutant enzyme W416G
5.9 - 46.3
propionate
11.9
valerate
-
65°C, mutant enzyme W416G
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.29 - 229
acetate
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
2.7
acetyl-CoA
-
pH 8.0
12
ADP
-
pH 8.0
15
AMP
-
pH 8.0
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.885
A0A144QFN1;
crude extract, at pH 8.0 and 37°C
7.4
-
Ni-activated A110C mutant alpha subunit at 1 atm CO
8.1
-
Ni-activated A222L mutant alpha subunit at 1 atm CO
11.9
AceCS2
13.4
-
formation of acetyl-CoA
26.8
AceCS1
52.873
A0A144QFN1;
after 59.7fold purification, at pH 8.0 and 37°C
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6.2
-
CO/acetyl-CoA exchange assay at
6.3
-
adenosine tetraphosphate synthesis
7.2
-
assay at
8.3 - 10.2
-
in 25 mM KCl buffer
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
5 - 9
-
isoform ACS1 shows high levels of activity in a pH range of 7.0-8.0. Isoform ACS2 shows high levels of activity in a pH range of 7.5-8.5. Little activity is detected for either isoform ACS1 or ACS2 at pH levels below 5.0 or above 9.0
5.5 - 8.5
-
pH 5.5: about 60% of maximal activity, pH 8.5: about 50% of maximal activity
6 - 10.5
-
6: about 50% of maximal activity, 10.5: about 60% of activity maximum
6 - 9.7
-
6.0: about 45% of maximal activity, 9.7: about 70% of maximal activity
6.5 - 8.5
-
30-40% of maximal activity at pH 6.5 and 8.5
6.8 - 10.1
-
about 50% of maximal activity at pH 6.8 and pH 10.1
6.8 - 8.8
-
about 50% of maximal activity at pH 6.8 and 8.8
7.3 - 8.1
-
90% of maximal activity at pH 7.3 and 8.1
7.5 - 10
-
7.5: about 50% of maximal activity, 10.0: about 70% of maximal activity
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
27
-
CO/acetyl-CoA exchange assay at
65 - 70
80
-
arsenolytic assay at and temperature optimum
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
15 - 55
-
the enzyme activity is more than 90% of maximum over a broad temperature range between 25 and 40°C, and both recombinant isoform proteins retain more than 60% of their maximum enzymatic activity at temperatures between 15 and 45°C. Isoform ACS1 enzyme activity decreases to 12% of its maximum at 55°C
20 - 50
-
20°C: about 45% of maximal activity, 50°C: about 30% of maximal activity
45 - 85
-
45°C: about 55% of maximal activity, 85°C: about 60% of maximal activity, AF-ACS2
45 - 75
45°C: about 55% of maximal activity, 75°C: about 50% of maximal activity
pI VALUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6
-
isoform ACS2, calculated from amino acid sequence
6.7
A0A144QFN1;
isoelectric focusing
8.1
-
isoform ACS1, calculated from amino acid sequence
8.7
-
isoform ACS2, isoelectric focusing
8.8
-
isoform ACS1, isoelectric focusing
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
marked induction of AceCS1 mRNA and protein during differentiation of 3T3-L1 cells, neither AceCS2 mRNA nor protein is detected in undifferentiated or differentiated 3T3-L1 cells
Manually annotated by BRENDA team
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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
Manually annotated by BRENDA team
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from Glycine max L. cv. Williams inoculated with Bradyrhizobium japonicum
Manually annotated by BRENDA team
-
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
Manually annotated by BRENDA team
-
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
Manually annotated by BRENDA team
-
the CRISPR/Cas9 system is used to create an ACLY-KO human fibroblast (HF) cell line called C9
Manually annotated by BRENDA team
-
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
Manually annotated by BRENDA team
-
newly-pupated pupae of both sexes
Manually annotated by BRENDA team
-
-
Manually annotated by BRENDA team
AceCS2, high activity
Manually annotated by BRENDA team
AceCS2, high activity
Manually annotated by BRENDA team
additional information
no AceCS2 activity is detected in liver. Marked induction of AceCS1 mRNA and protein during differentiation of 3T3-L1 cells, neither AceCS2 mRNA nor protein is detected in undifferentiated or differentiated 3T3-L1 cells
Manually annotated by BRENDA team