Information on EC 2.3.3.10 - hydroxymethylglutaryl-CoA synthase

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

EC NUMBER
COMMENTARY hide
2.3.3.10
-
RECOMMENDED NAME
GeneOntology No.
hydroxymethylglutaryl-CoA synthase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
acetyl-CoA + H2O + acetoacetyl-CoA = (S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
-
-
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Acyl group transfer
condensation
hydrolysis
-
-
-
-
transacetylation
-
-
-
-
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
Biosynthesis of antibiotics
-
-
Biosynthesis of secondary metabolites
-
-
Butanoate metabolism
-
-
ferrichrome A biosynthesis
-
-
isoprene biosynthesis II (engineered)
-
-
ketogenesis
-
-
Metabolic pathways
-
-
mevalonate pathway I
-
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mevalonate pathway II (archaea)
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mevalonate pathway III (archaea)
-
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Synthesis and degradation of ketone bodies
-
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Terpenoid backbone biosynthesis
-
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Valine, leucine and isoleucine degradation
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mevalonate metabolism
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SYSTEMATIC NAME
IUBMB Comments
acetyl-CoA:acetoacetyl-CoA C-acetyltransferase (thioester-hydrolysing, carboxymethyl-forming)
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CAS REGISTRY NUMBER
COMMENTARY hide
9027-44-5
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
UniProt
Manually annotated by BRENDA team
BjHMGS1
-
-
Manually annotated by BRENDA team
BjHMGS2
-
-
Manually annotated by BRENDA team
BjHMGS3
-
-
Manually annotated by BRENDA team
BjHMGS4
-
-
Manually annotated by BRENDA team
-
SwissProt
Manually annotated by BRENDA team
-
UniProt
Manually annotated by BRENDA team
guinea pig
-
-
Manually annotated by BRENDA team
-
UniProt
Manually annotated by BRENDA team
pigeon
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
UniProt
Manually annotated by BRENDA team
-
SwissProt
Manually annotated by BRENDA team
-
SwissProt
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
UniProt
Manually annotated by BRENDA team
turkey
-
-
Manually annotated by BRENDA team
hydroxymethylglutaryl-CoA synthase is transcriptionally regulated by isovalerate
-
-
Manually annotated by BRENDA team
no activity in Streptomyces albus
-
-
-
Manually annotated by BRENDA team
-
UniProt
Manually annotated by BRENDA team
-
UniProt
Manually annotated by BRENDA team
radish
-
-
Manually annotated by BRENDA team
Sprague-Dawley
-
-
Manually annotated by BRENDA team
-
UniProt
Manually annotated by BRENDA team
-
UniProt
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
UniProt
Manually annotated by BRENDA team
-
UniProt
Manually annotated by BRENDA team
Vitis vinifera x Vitis vinifera
-
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
metabolism
-
3-hydroxy-3-methylglutaryl-CoA synthase is the second enzyme in the cytosolic mevalonate pathway
physiological function
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
3-oxobutyryl-CoA + acetoacetyl-CoA + H2O
3-hydroxy-3-methyl-5-oxoheptanedioyl-CoA + CoA
show the reaction diagram
-
-
-
-
?
acetyl-3'-dephospho-CoA + acetoacetyl-CoA + H2O
3-hydroxy-3-methylglutaryl-CoA + 3'-dephospho-CoA
show the reaction diagram
acetyl-CoA + 3'-dephospho-CoA + H2O
acetyldephospho-CoA + CoA
show the reaction diagram
acetyl-CoA + acetoacetyl-ACP + H2O
3-hydroxy-3-methylglutaryl-ACP
show the reaction diagram
-
-
-
-
?
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
acetyl-CoA + cysteamine + H2O
? + CoA
show the reaction diagram
-
-
-
-
?
acetyl-CoA + H2O
acetate + CoA
show the reaction diagram
acetyl-CoA + H2O + acetoacetyl-CoA
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
acetyl-CoA + N-acetyl-S-acetoacetylcysteamine + H2O
? + CoA
show the reaction diagram
-
-
-
-
?
acetylglutathione + acetoacetyl-CoA + H2O
?
show the reaction diagram
-
-
-
-
?
acetylpantetheine + acetoacetyl-CoA + H2O
3-hydroxy-3-methylglutaryl-CoA + pantetheine
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
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
acetyl-CoA + H2O + acetoacetyl-CoA
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
additional information
?
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
KCl
optimal concentration
Mn2+
-
increases acetoacetate synthesis activity
additional information
-
no stimulation by Mg2+, Mn2+, Zn2+ and Co2+
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(E,E)-11-(3-hydroxymethyl-4-oxo-2-oxytanyl)-3,5,7-trimethyl-2,4-undecadienoic acid
-
i.e. F-244
(E,E)-11-[3-(hydroxymethyl)-4-oxo-2-oxytanyl]-3,5,7-trimethyl-2,4-undecadienenoic acid
(S)-3-hydroxy-3-methylglutaryl-CoA
-
-
1-ethyl-3-(3-dimethylaminopropyl)carbodiimide
2-benzyl-9-(3,6-dioxocyclohexa-1,4-dienyl)-2,3,7,8-tetrahydro-6H-pyrido[1,2-a]pyrazine-1,4-dione
-
-
3,3'-dimethylglutaryl-CoA
-
-
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3-carboxy-2,2,5,5,-tetramethyl-1-pyrrolidinyloxyl-CoA
-
-
3-carboxypropionyl-CoA
-
-
3-Chloropropionyl-CoA
3-hydroxy-3-methylglutaryl-CoA
-
-
3-oxohexanoyl-CoA
-
-
5,5'-dithiobis(2-nitrobenzoate)
acetoacetyl-CoA
acetyloxy(phenyl)mercury
-
phenyl mercuric acetate
arsenite
-
in presence of CoA, residual activity 25%
Bromoacetyl-CoA
-
-
CdSO4
-
residual activity 9%
decanoyl-CoA
-
-
diethylcarbamothioylsulfanyl N,N-diethylcarbamodithioate
-
disulfiram
DL-3-hydroxy-3-methylglutaryl-CoA
DL-3-methylglutaryl-CoA
-
-
glutaryl-CoA
-
-
heptanoyl-CoA
-
-
Hexanoyl-CoA
-
-
hymeglusin
iodoacetamide
L-659,699
Lifibrol
Mg2+
-
mitochondrial enzyme
MgCl2
N-ethylmaleimide
NaAsO2
-
residual activity 90%
nonanoyl-CoA
-
-
Octanoyl-CoA
-
-
p-chloromercuribenzoate
palmitoyl-CoA
-
mitochondrial synthase
phenyl arsenious oxide
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in presence of CoA, residual activity 41%; residual activity 75%
propionyl-CoA
-
-
succinyl-CoA
additional information
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
dithioerythritol
-
5 mM, activates
MgCl2
potassium phosphate
-
-
Sodium phosphate
-
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.019 - 0.116
3-oxobutyl-CoA
-
0.0001 - 0.115
acetoacetyl-CoA
0.0015 - 1.561
acetyl-CoA
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0017 - 4.6
acetyl-CoA
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
92
acetyl-CoA
Haloferax volcanii
D4GWR6
pH 8.0, 30°C
29
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.009 - 0.0389
(S)-3-hydroxy-3-methylglutaryl-CoA
0.12
3,3'-dimethylglutaryl-CoA
-
pH 8.0
-
0.015
3-Chloropropionyl-CoA
-
-
0.0011 - 0.0031
3-hydroxy-3-methylglutaryl-CoA
0.0071 - 0.014
3-oxohexanoyl-CoA
0.00126 - 0.242
acetoacetyl-CoA
0.033
butyryl-CoA
-
pH 8.0
0.038 - 0.08
CoA
0.0027
decanoyl-CoA
-
pH 8.0
0.03 - 0.07
desulfo-CoA
0.012 - 0.013
DL-3-hydroxy-3-methylglutaryl-CoA
0.1
DL-3-methylglutaryl-CoA
-
pH 8.0
0.11
glutaryl-CoA
-
pH 8.0
0.0123
heptanoyl-CoA
-
pH 8.0
0.022
Hexanoyl-CoA
-
pH 8.0
0.00057 - 0.7
hymeglusin
0.0000537
L-659,699
-
-
0.004
nonanoyl-CoA
-
pH 8.0
0.0081
Octanoyl-CoA
-
pH 8.0
0.0005
palmityl-CoA
-
-
0.005
propionyl-CoA
-
pH 8.0
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.000035
F-244
Brassica juncea
-
IC50: 35 nM
0.00032
hymeglusin
Cricetinae
-
IC50: 0.00032 mM, inhibitor binds to the thiol residue of Cys
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.00083
-
mitochondrial pellet
0.00133
-
mitochondrial pellet, 0.25 M sucrose
0.00245
-
disrupted mitochondria, 0.25 M sucrose
0.00288
-
mitochondrial pellet, 0.50 M sucrose
0.00325
-
mitochondrial pellet, 0.88 M sucrose
0.00485
-
homogenate
0.00567
-
disrupted mitochondria, 0.50 M sucrose
0.00792
-
disrupted mitochondria, 0.88 M sucrose
0.00922
-
mitochondrial supernatant
0.00958
-
mitochondrial supernatant, 0.88 M sucrose
0.0101
-
-
0.01053
-
mitochondrial supernatant, 0.50 M sucrose
0.0111
-
mitochondrial supernatant, 0.25 M sucrose
0.035
activity in response to acetaminophen, APAP, treatment
0.057
control, no acetaminophen, APAP, treatment
0.5 - 1
-
liver enzyme
0.65
-
cytoplasmic enzyme, isozyme III and IV
0.76
-
-
0.8 - 1
-
recombinant enzyme
0.88
-
-
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
8.2
activity assay
9.2
-
synthase II
9.3
-
synthase I
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.5 - 9.5
-
pH 7.5: about 60% of maximal activity, pH 9.5: about 30% of maximal activity
7.75 - 9.5
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-
8 - 9.6
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
24
-
activity assay, A412 nm assay
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
30 - 45
-
about 70% of maximal activity at 30°C and at 45°C
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
enzyme is a direct target of c-Myc, which represses hydroxymethylglutaryl-CoA synthase transcriptional activity
Manually annotated by BRENDA team
-
developmental regulation
Manually annotated by BRENDA team
-
of adults
Manually annotated by BRENDA team
-
HMGS2 is well expressed
Manually annotated by BRENDA team
-
-
Manually annotated by BRENDA team
anterior midgut, topically applied juvenile hormone III induced enzyme mRNA levels up to 6.5fold
Manually annotated by BRENDA team
-
HMGS2 is well expressed
Manually annotated by BRENDA team
lowest expression
Manually annotated by BRENDA team
-
developmental regulation
Manually annotated by BRENDA team
highest expression
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE