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
2.3.3.10
-
RECOMMENDED NAME
GeneOntology No.
hydroxymethylglutaryl-CoA synthase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
acetyl-CoA + H2O + acetoacetyl-CoA = (S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Acyl group transfer
-
-
-
-
Acyl group transfer
P22791
-
condensation
-
-
-
-
condensation
-
-
condensation
P54869
-
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 metabolism
-
-
mevalonate pathway I
-
-
mevalonate pathway II (archaea)
-
-
mevalonate pathway III (archaea)
-
-
Synthesis and degradation of ketone bodies
-
-
Terpenoid backbone biosynthesis
-
-
Valine, leucine and isoleucine degradation
-
-
SYSTEMATIC NAME
IUBMB Comments
acetyl-CoA:acetoacetyl-CoA C-acetyltransferase (thioester-hydrolysing, carboxymethyl-forming)
-
SYNONYMS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
(S)-3-hydroxy-3-methylglutaryl-CoA acetoacetyl-CoA-lyase (CoA-acetylating)
-
-
-
-
3-hydroxy-3-methylglutaryl CoA synthase
D4GWR6
-
3-hydroxy-3-methylglutaryl CoA synthase
Haloferax volcanii DSM 3757
D4GWR6
-
-
3-hydroxy-3-methylglutaryl CoA synthetase
-
-
-
-
3-hydroxy-3-methylglutaryl coenzyme A synthase
-
-
-
-
3-hydroxy-3-methylglutaryl coenzyme A synthase
-
-
3-hydroxy-3-methylglutaryl coenzyme A synthase
D4GWR6
-
3-hydroxy-3-methylglutaryl coenzyme A synthase
Haloferax volcanii DSM 3757
D4GWR6
-
-
3-hydroxy-3-methylglutaryl coenzyme A synthase
P54868, Q01581
-
3-hydroxy-3-methylglutaryl coenzyme A synthase
-
-
3-hydroxy-3-methylglutaryl coenzyme A synthetase
-
-
-
-
3-hydroxy-3-methylglutaryl-CoA synthase
-
-
-
-
3-hydroxy-3-methylglutaryl-CoA synthase
-
-
3-hydroxy-3-methylglutaryl-CoA synthase
-
-
3-hydroxy-3-methylglutaryl-CoA synthase
-
-
3-hydroxy-3-methylglutaryl-CoA synthase
-
-
3-hydroxy-3-methylglutaryl-CoA synthase
-
-
3-hydroxy-3-methylglutaryl-CoA synthase
-
-
3-hydroxy-3-methylglutaryl-CoA synthase 1
-
-
3-hydroxy-3-methylglutaryl-CoA synthase 2
P54869
-
3-hydroxy-3-methylglutaryl-coenzyme A synthase
-
-
-
-
3-hydroxy-3-methylglutaryl-coenzyme A synthase
P22791
-
3-hydroxyl-3-methyl-glutaryl-CoA synthase
-
-
acetoacetyl coenzyme A transacetase
-
-
-
-
beta-hydroxy-beta-methylglutaryl-CoA synthase
-
-
-
-
BjHMGS1
-
-
BjHMGS1
Brassica juncea BjHMGS1, Brassica juncea BjHMGS2, Brassica juncea BjHMGS3, Brassica juncea BjHMGS4
-
-
-
BjHMGS2
-
-
BjHMGS2
Brassica juncea BjHMGS1, Brassica juncea BjHMGS2, Brassica juncea BjHMGS3, Brassica juncea BjHMGS4
-
-
-
BjHMGS3
-
-
BjHMGS3
Brassica juncea BjHMGS1, Brassica juncea BjHMGS2, Brassica juncea BjHMGS3, Brassica juncea BjHMGS4
-
-
-
BjHMGS4
-
-
BjHMGS4
Brassica juncea BjHMGS1, Brassica juncea BjHMGS2, Brassica juncea BjHMGS3, Brassica juncea BjHMGS4
-
-
-
EC 4.1.3.5
-
-
formerly
-
HMG-CoA
-
-
HMG-CoA synthase
-
-
-
-
HMG-CoA synthase
-
-
HMG-CoA synthase
Brassica juncea BjHMGS1, Brassica juncea BjHMGS2, Brassica juncea BjHMGS3, Brassica juncea BjHMGS4
-
-
-
HMG-CoA synthase
-
-
HMG-CoA synthase
Q9FD71
-
HMG-CoA synthase
-
-
HMG-CoA synthase
P54868, Q01581
-
HMG-CoA synthase
P54869
-
HMG-CoA synthase
-
-
HMG-CoA synthase
P22791
-
HMG-CoA synthase 1
-
-
HMG-CoS synthase
-
-
HMGCS
D4GWR6
-
HMGCS
Haloferax volcanii DSM 3757
D4GWR6
-
-
HMGCS
P54868, Q01581
-
HMGCS1
Q01581
isoform
HMGCS2
P54868
isoform
HMGCS2
P22791
-
HMGS
Vitis vinifera x Vitis riparia, Vitis vinifera x Vitis vinifera
-
-
hydroxymethylglutaryl CoA synthetase
-
-
-
-
hydroxymethylglutaryl coenzyme A synthase
-
-
-
-
hydroxymethylglutaryl coenzyme A synthase
Vitis vinifera x Vitis riparia, Vitis vinifera x Vitis vinifera
-
-
hydroxymethylglutaryl coenzyme A-condensing enzyme
-
-
-
-
hydroxymethylglutaryl-CoA synthase
P22791
-
hydroxymethylglutaryl-coenzyme A synthase
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
9027-44-5
-
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
cockroach, cytosolic isoform 1
SwissProt
Manually annotated by BRENDA team
cockroach, cytosolic isoform 2
SwissProt
Manually annotated by BRENDA team
BjHMGS1; BjHMGS2; BjHMGS3; BjHMGS4
-
-
Manually annotated by BRENDA team
Brassica juncea BjHMGS1
BjHMGS1
-
-
Manually annotated by BRENDA team
Brassica juncea BjHMGS2
BjHMGS2
-
-
Manually annotated by BRENDA team
Brassica juncea BjHMGS3
BjHMGS3
-
-
Manually annotated by BRENDA team
Brassica juncea BjHMGS4
BjHMGS4
-
-
Manually annotated by BRENDA team
guinea pig
-
-
Manually annotated by BRENDA team
pigeon
-
-
Manually annotated by BRENDA team
chinese hamster, cytosolic isoform
SwissProt
Manually annotated by BRENDA team
avian; chicken
-
-
Manually annotated by BRENDA team
chicken, cytosolic isoform
SwissProt
Manually annotated by BRENDA team
chicken; white Leghorn cockerels
-
-
Manually annotated by BRENDA team
Haloferax volcanii DSM 3757
-
SwissProt
Manually annotated by BRENDA team
HeLa cells
-
-
Manually annotated by BRENDA team
HepG2 cells
-
-
Manually annotated by BRENDA team
human, cytosolic isoform
SwissProt
Manually annotated by BRENDA team
human, mitochondrial isoform
SwissProt
Manually annotated by BRENDA team
isoform HMGCS1
SwissProt
Manually annotated by BRENDA team
isoform HMGCS2
-
-
Manually annotated by BRENDA team
isoform HMGCS2
SwissProt
Manually annotated by BRENDA team
-
SwissProt
Manually annotated by BRENDA team
syrian hamster, golden hamster
-
-
Manually annotated by BRENDA team
-
SwissProt
Manually annotated by BRENDA team
mouse, mitochondrial isoform
SwissProt
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
rat, cytosolic isoform
SwissProt
Manually annotated by BRENDA team
rat, mitochondrial isoform
SwissProt
Manually annotated by BRENDA team
rat; Sprague-Dawley
-
-
Manually annotated by BRENDA team
Sprague-Dawley
-
-
Manually annotated by BRENDA team
stroke-prone spontaneously hypertensive rats, SHRSPs, and their ancestral hypertensive but stroke-resistant spontaneously hypertensive rats, SHRs
SwissProt
Manually annotated by BRENDA team
Rattus norvegicus Sprague-Dawley
Sprague-Dawley
-
-
Manually annotated by BRENDA team
baker's yeast
SwissProt
Manually annotated by BRENDA team
pig
-
-
Manually annotated by BRENDA team
pig, mitochondrial isoform
SwissProt
Manually annotated by BRENDA team
piglet
-
-
Manually annotated by BRENDA team
Vitis vinifera x Vitis riparia
-
-
-
Manually annotated by BRENDA team
Vitis vinifera x Vitis vinifera
-
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
metabolism
-
3-hydroxy-3-methylglutaryl-CoA synthase is the second enzyme in the cytosolic mevalonate pathway
physiological function
Vitis vinifera x Vitis vinifera, Vitis vinifera x Vitis riparia
-
involved in terpenoid metabolism
physiological function
-
enzyme overexpression up-regulates 3-hydroxy-3-methylglutaryl-CoA reductase, sterol methyltransferase 2, delta-24 sterol reductase, C-22 sterol desaturase, and brassinosteroid-6-oxidase 2, leading to enhanced sterol content and stress tolerance in Arabidopsis. Enzyme overexpressing Arabidopsis seeds germinate approximately 1 day earlier than wild type seeds. Enzyme overexpressing Arabidopsis seedlings show enhanced resistance to Botrytis cinerea, and detached leaves are delayed in H2O2-induced cell death
physiological function
D4GWR6
the enzyme is involved in the mevalonate pathway in archaea. Archaea are characterized by cell membrane lipids that contain, as a major component, polyisoprenoids in ether linkages to glycerol rather than the ester-linked fatty acids that characterize membranes of other organisms. Archaeal polyisoprenoids derive from isopentenyl 5-diphosphate produced by enzymes of the mevalonate pathway
physiological function
Haloferax volcanii DSM 3757
-
the enzyme is involved in the mevalonate pathway in archaea. Archaea are characterized by cell membrane lipids that contain, as a major component, polyisoprenoids in ether linkages to glycerol rather than the ester-linked fatty acids that characterize membranes of other organisms. Archaeal polyisoprenoids derive from isopentenyl 5-diphosphate produced by enzymes of the mevalonate pathway
-
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
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-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 + 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 + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
-
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
-
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
-
-
ir
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
-
-
-
ir
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
P23228
-
-
-
ir
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
-
-
-
ir
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
-
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
-
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
-
-
-
?
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
-
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
-
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
-
-
-
?
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
P54868, Q01581
-
-
-
ir
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
-
-
-
ir
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
-
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
-
-
-
ir
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
-
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
-
-
ir
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
-
-
ir
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
P54839
-
-
-
ir
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
-
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
-
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
-
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
-
-
-
ir
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
-
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
-
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
-
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
-
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
-
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
-
-
-
?
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
-
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
-
-
-
?
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
-
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
-
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
P54873
-
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
-
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
P54870, P54961
-
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
-
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
O51626
-
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
-
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
P54871
-
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
P13704
-
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
-
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
-
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
P23228
-
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
P54868, Q01581
-
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
P54868, Q01581
-
-
-
?
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
P54869
-
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
-
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
P93773
-
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
-
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
P17425, P22791
-
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
-
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
P54839
-
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
P54874
-
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
-
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
O02734
-
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
-
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
Q9FD71
-
-
-
?
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
cytosolic synthase catalyzes the second step of cholesterogenesis from acetyl-CoA
-
ir
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
produces a key intermediate in steroidogenic and ketogenic metabolic pathways
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
isopentenyl diphosphate biosynthesis
-
-
ir
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
mitochondrial enzyme is involved in the synthesis of acetoacetate, cytoplasmic enzyme in that of mevalonate
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
commited step in the pathways for isoprenoid, cholesterol and ketone body production, cytosolic isoform involved in isoprenoid/cholesterol biosynthesis
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
mitochondrial enzyme of liver functions in ketogenesis, its cytoplasmic counterpart participates in cholesterogenesis
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
mitochondrial enzyme of liver functions in ketogenesis, its cytoplasmic counterpart participates in cholesterogenesis
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
mitochondrial enzyme of liver functions in ketogenesis, its cytoplasmic counterpart participates in cholesterogenesis
-
ir
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
mitochondrial enzyme of liver functions in ketogenesis, its cytoplasmic counterpart participates in cholesterogenesis
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
first committed step in isoprenoid biosynthesis
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
pathway converting acetyl-CoA to ketone bodies
-
-
ir
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
synthesis of isoprenes and steroids
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
synthesis of isoprenes and steroids
-
ir
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
regulation of isoprenoid synthesis and metabolism
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
enzyme involved in ketone body production, control of hepatic fatty acid oxidation, potential control point for ketogenesis
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
pathway of ketogenesis in the mitochondria, mevalonate synthesis in the cytoplasm
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
P23228
key intermediate in cholesterogenic and ketogenic pathways, cholesterogenic isoform in cytosol, ketogenic isoform in mitochondria, committed step for both pathways
-
-
ir
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
P54868, Q01581
key intermediate in cholesterogenic and ketogenic pathways, cholesterogenic isoform in cytosol, ketogenic isoform in mitochondria, committed step for both pathways
-
-
ir
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
P54839
key intermediate in cholesterogenic and ketogenic pathways, cholesterogenic isoform in cytosol, ketogenic isoform in mitochondria, committed step for both pathways
-
-
ir
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
key role in synthesis of various sterols and isoprenoids
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
major cytoplasmic synthase, synthase II is implicated in cholesterol synthesis
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
acetoacetate biosynthesis, 3-hydroxy-3-methylglutaryl-CoA pathway
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
mevalonate pathway
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
potentially favorable position for the regulation of hepatic ketogenesis
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
second enzyme in the cytoplasmic mevalonate pathway of isoprenoid biosynthesis
-
-
?
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
the enzyme catalyzes the first committed step in the mevalonate pathway
-
-
?
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
the enzyme is down-regulated by abscisic acid, osmotic stress and dehydration
-
-
?
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
Rattus norvegicus Sprague-Dawley
-
-
-
-
-
acetyl-CoA + cysteamine + H2O
? + CoA
show the reaction diagram
-
-
-
-
?
acetyl-CoA + H2O
acetate + CoA
show the reaction diagram
-
-
-
?
acetyl-CoA + H2O
acetate + CoA
show the reaction diagram
P23228
-
-
-
?
acetyl-CoA + H2O
acetate + CoA
show the reaction diagram
-
-
-
-
?
acetyl-CoA + H2O
acetate + CoA
show the reaction diagram
-
in absence of co-substrate enzyme hydrolyzes acetyl-CoA
-
-
?
acetyl-CoA + H2O + acetoacetyl-CoA
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
-
-
-
ir
acetyl-CoA + H2O + acetoacetyl-CoA
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
P54869
-
-
-
ir
acetyl-CoA + H2O + acetoacetyl-CoA
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
P22791
-
-
-
?
acetyl-CoA + H2O + acetoacetyl-CoA
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
D4GWR6
the enzyme is involved in the mevalonate pathway. Archaea are characterized by cell membrane lipids that contain, as a major component, polyisoprenoids in ether linkages to glycerol rather than the ester-linked fatty acids that characterize membranes of other organisms. Archaeal polyisoprenoids derive from isopentenyl 5-diphosphate produced by enzymes of the mevalonate pathway
-
-
?
acetyl-CoA + H2O + acetoacetyl-CoA
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
Haloferax volcanii DSM 3757
D4GWR6
the enzyme is involved in the mevalonate pathway. Archaea are characterized by cell membrane lipids that contain, as a major component, polyisoprenoids in ether linkages to glycerol rather than the ester-linked fatty acids that characterize membranes of other organisms. Archaeal polyisoprenoids derive from isopentenyl 5-diphosphate produced by enzymes of the mevalonate pathway
-
-
?
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
?
-
-
-
-
-
-
additional information
?
-
-
-
-
-
-
additional information
?
-
-
acetyl-CoA homologues do not act as substrates
-
-
-
additional information
?
-
-
feeding cholestyramine to rats causes a 2.6fold increase in the cytosolic activities of the synthase in liver
-
-
-
additional information
?
-
-
acetyl-CoA analogues can act as substrates, acetoacyl-analogues are no substrates
-
-
-
additional information
?
-
-
absolutely specific for the acyl-moiety of both its substrates, neither propionyl- nor butyryl CoA can replace acetyl-CoA
-
-
-
additional information
?
-
-
reaction is stereospecific and associated with an intramolecular hydrogen isotope effect, condensation proceeds with inversion of configuration at the methyl group
-
-
-
additional information
?
-
-
cholesterol feeding causes a significant reduction in the HMG-CoA synthase activity of the cytosolic fraction of liver
-
-
-
additional information
?
-
-
absolutely specific for acetyl-CoA and acetoacetyl-CoA in the reaction, neither propionyl- nor butyryl-CoA can replace acetyl-CoA, no reaction observed when 3-oxohexanoyl-CoA is substituted for acetoacetyl-CoA
-
-
-
additional information
?
-
-
first organism known to have 2 functional cytosolic HMG-CoA synthases
-
-
-
additional information
?
-
-
enzyme activity and mRNA levels are upregulated after 3-thia fatty acid treatment
-
-
-
additional information
?
-
-
hydroxymethylglutaryl-CoA synthase is involved in an alternative pathway for isovaleryl-coA synthesis
-
-
-
additional information
?
-
-
the natural variant (V227A) of peroxisome proliferator-activated receptor-alpha (PPARalpha) significantly attenuates PPARalpha-mediated transactivation of the cytochrome P450 4A6 and mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase (HMGCS2) genes in the presence of fibrate ligands
-
-
-
additional information
?
-
P54868, Q01581
the enzyme catalyzes a three-step ping-pong reaction involving an acylation, a condensation, and a hydrolysis
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
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 + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
-
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
-
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
-
-
-
ir
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
-
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
-
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
-
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
-
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
-
-
-
ir
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
-
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
-
-
-
ir
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
-
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
-
-
ir
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
-
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
-
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
-
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
-
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
-
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
-
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
-
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
-
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
-
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
-
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
P54873
-
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
-
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
P54870, P54961
-
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
-
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
O51626
-
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
-
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
P54871
-
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
P13704
-
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
-
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
-
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
P23228
-
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
P54868, Q01581
-
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
P54869
-
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
-
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
P93773
-
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
-
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
P17425, P22791
-
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
-
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
P54839
-
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
P54874
-
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
-
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
O02734
-
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
-
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
cytosolic synthase catalyzes the second step of cholesterogenesis from acetyl-CoA
-
ir
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
produces a key intermediate in steroidogenic and ketogenic metabolic pathways
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
isopentenyl diphosphate biosynthesis
-
-
ir
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
mitochondrial enzyme is involved in the synthesis of acetoacetate, cytoplasmic enzyme in that of mevalonate
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
commited step in the pathways for isoprenoid, cholesterol and ketone body production, cytosolic isoform involved in isoprenoid/cholesterol biosynthesis
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
mitochondrial enzyme of liver functions in ketogenesis, its cytoplasmic counterpart participates in cholesterogenesis
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
mitochondrial enzyme of liver functions in ketogenesis, its cytoplasmic counterpart participates in cholesterogenesis
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
mitochondrial enzyme of liver functions in ketogenesis, its cytoplasmic counterpart participates in cholesterogenesis
-
ir
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
mitochondrial enzyme of liver functions in ketogenesis, its cytoplasmic counterpart participates in cholesterogenesis
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
first committed step in isoprenoid biosynthesis
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
pathway converting acetyl-CoA to ketone bodies
-
-
ir
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
synthesis of isoprenes and steroids
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
synthesis of isoprenes and steroids
-
ir
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
regulation of isoprenoid synthesis and metabolism
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
enzyme involved in ketone body production, control of hepatic fatty acid oxidation, potential control point for ketogenesis
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
pathway of ketogenesis in the mitochondria, mevalonate synthesis in the cytoplasm
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
P23228
key intermediate in cholesterogenic and ketogenic pathways, cholesterogenic isoform in cytosol, ketogenic isoform in mitochondria, committed step for both pathways
-
-
ir
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
P54868, Q01581
key intermediate in cholesterogenic and ketogenic pathways, cholesterogenic isoform in cytosol, ketogenic isoform in mitochondria, committed step for both pathways
-
-
ir
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
P54839
key intermediate in cholesterogenic and ketogenic pathways, cholesterogenic isoform in cytosol, ketogenic isoform in mitochondria, committed step for both pathways
-
-
ir
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
key role in synthesis of various sterols and isoprenoids
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
major cytoplasmic synthase, synthase II is implicated in cholesterol synthesis
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
acetoacetate biosynthesis, 3-hydroxy-3-methylglutaryl-CoA pathway
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
mevalonate pathway
-
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
potentially favorable position for the regulation of hepatic ketogenesis
-
-
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
second enzyme in the cytoplasmic mevalonate pathway of isoprenoid biosynthesis
-
-
?
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
the enzyme catalyzes the first committed step in the mevalonate pathway
-
-
?
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
the enzyme is down-regulated by abscisic acid, osmotic stress and dehydration
-
-
?
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
Rattus norvegicus Sprague-Dawley
-
-
-
-
-
acetyl-CoA + H2O + acetoacetyl-CoA
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
-
-
-
ir
acetyl-CoA + H2O + acetoacetyl-CoA
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
P54869
-
-
-
ir
acetyl-CoA + H2O + acetoacetyl-CoA
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
P22791
-
-
-
?
acetyl-CoA + H2O + acetoacetyl-CoA
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
Haloferax volcanii, Haloferax volcanii DSM 3757
D4GWR6
the enzyme is involved in the mevalonate pathway. Archaea are characterized by cell membrane lipids that contain, as a major component, polyisoprenoids in ether linkages to glycerol rather than the ester-linked fatty acids that characterize membranes of other organisms. Archaeal polyisoprenoids derive from isopentenyl 5-diphosphate produced by enzymes of the mevalonate pathway
-
-
?
additional information
?
-
-
enzyme activity and mRNA levels are upregulated after 3-thia fatty acid treatment
-
-
-
additional information
?
-
-
hydroxymethylglutaryl-CoA synthase is involved in an alternative pathway for isovaleryl-coA synthesis
-
-
-
additional information
?
-
-
the natural variant (V227A) of peroxisome proliferator-activated receptor-alpha (PPARalpha) significantly attenuates PPARalpha-mediated transactivation of the cytochrome P450 4A6 and mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase (HMGCS2) genes in the presence of fibrate ligands
-
-
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
CoA
P22791
-
CoA
P54869
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
KCl
D4GWR6
optimal concentration
Mg2+
-
cytoplasmic enzyme
Mg2+
-
activity of the recombinant cytosolic isozyme ist stimulated by
Mn2+
-
increases acetoacetate synthesis activity
additional information
-
no stimulation by Mg2+, Mn2+, Zn2+ and Co2+
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY
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
-
-
(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
-
-
1-ethyl-3-(3-dimethylaminopropyl)carbodiimide
Q01581
-
1-ethyl-3-(3-dimethylaminopropyl)carbodiimide
P54839
-
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
-
-
-
3-carboxy-2,2,5,5,-tetramethyl-1-pyrrolidinyloxyl-CoA
-
-
3-carboxypropionyl-CoA
-
-
3-Chloropropionyl-CoA
-
-
3-Chloropropionyl-CoA
-
-
3-hydroxy-3-methylglutaryl-CoA
-
-
3-Oxohexanoyl-CoA
-
-
5,5'-dithiobis(2-nitrobenzoate)
-
residual activity 51%
5,5'-dithiobis(2-nitrobenzoate)
-
Ellman's reagent
5,5'-dithiobis(2-nitrobenzoate)
-
-
acetoacetyl-CoA
-
substrate inhibition
acetoacetyl-CoA
-
substrate inhibition
acetoacetyl-CoA
-
competitive inhibition
acetoacetyl-CoA
-
-
acetoacetyl-CoA
-
-
acetoacetyl-CoA
-
-
acetoacetyl-CoA
-
inhibition of wild-type enzyme, no inhibition of mutant enzyme H188N and H188N/S259A
acetoacetyl-CoA
-
potent inhibitor of the overall reaction
acetoacetyl-CoA
-
substrate inhibition
acetyloxy(phenyl)mercury
-
phenyl mercuric acetate
arsenite
-
in presence of CoA, residual activity 25%
Bromoacetyl-CoA
-
-
CdSO4
-
residual activity 9%
CoA
-
-
CoA
-
mixed product inhibition
decanoyl-CoA
-
-
diethylcarbamothioylsulfanyl N,N-diethylcarbamodithioate
-
disulfiram
DL-3-hydroxy-3-methylglutaryl-CoA
-
uncompetitive inhibition
DL-3-hydroxy-3-methylglutaryl-CoA
-
mixed product inhibition
DL-3-hydroxy-3-methylglutaryl-CoA
-
-
DL-3-hydroxy-3-methylglutaryl-CoA
-
product inhibition
DL-3-hydroxy-3-methylglutaryl-CoA
-
competitive inhibition
DL-3-methylglutaryl-CoA
-
-
F-244
-
IC50: 35 nM
glutaryl-CoA
-
-
Heptanoyl-CoA
-
-
Hexanoyl-CoA
-
-
hymeglusin
-
IC50: 0.00032 mM, inhibitor binds to the thiol residue of Cys
hymeglusin
-
-
hymeglusin
-
-
hymeglusin
Q9FD71
i.e. (2E,4E,7R)-11-[(2R,3R)-3-(hydroxymethyl)-4-oxooxetan-2-yl]-3,5,7-trimethylundeca-2,4-dienoic acid, time-dependent loss of activity is observed with more than 95% inhibition achieved at extended incubation times (10 min at 75-600 nM)
hymeglusin
D4GWR6
-
iodoacetamide
-
residual activity 84%
iodoacetamide
-
-
L-659,699
-
antibiotic 1233A
L-659,699
-
potent inhibitor of the recombinant enzyme
L-659,699
-
-
methanol
D4GWR6
-
Mg2+
-
mitochondrial enzyme
MgCl2
-
synthase I
MgCl2
-
mitochondrial enzyme
N-ethylmaleimide
-
residual activity 46%
N-ethylmaleimide
-
-
NaAsO2
-
residual activity 90%
Nonanoyl-CoA
-
-
Octanoyl-CoA
-
-
p-chloromercuribenzoate
-
residual activity 16%
p-chloromercuribenzoate
-
-
p-chloromercuribenzoate
-
-
palmitoyl-CoA
-
mitochondrial synthase
phenyl arsenious oxide
-
in presence of CoA, residual activity 41%; residual activity 75%
propionyl-CoA
-
-
succinyl-CoA
-
mitochondrial synthase, 50% inhibition
succinyl-CoA
-
-
additional information
-
desulfo-CoA protects against bromoacetyl-CoA inhibition, but not against p-chloromercuribenzoate and N-ethylmaleimide
-
additional information
D4GWR6
insensitive to feedback substrate inhibition by acetoacetyl-CoA
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
dithioerythritol
-
5 mM, activates
MgCl2
-
small activating effect on synthases II and III
MgCl2
-
optimal activity in 2.0 mM
MgCl2
-
-
potassium phosphate
-
-
Sodium phosphate
-
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.019
3-oxobutyl-CoA
-
-
-
0.021
3-oxobutyl-CoA
-
-
-
0.116
3-oxobutyl-CoA
-
mutant H264A
-
0.0001
acetoacetyl-CoA
-
-
0.00035
acetoacetyl-CoA
-
-
0.0004
acetoacetyl-CoA
-
pH 8.0
0.00055
acetoacetyl-CoA
-
mutant H197N
0.00062
acetoacetyl-CoA
-
mutant H436N
0.00085
acetoacetyl-CoA
-
-
0.00119
acetoacetyl-CoA
-
-
0.0012
acetoacetyl-CoA
-
-
0.0014
acetoacetyl-CoA
D4GWR6
pH 8.0, 30C
0.002
acetoacetyl-CoA
-
cytoplasmic isozymes I-IV
0.0029
acetoacetyl-CoA
-
pH 7.5, 30C, mutant enzyme H188N/S359A
0.003
acetoacetyl-CoA
-
pH 8.9
0.0032
acetoacetyl-CoA
-
pH 8.9
0.005
acetoacetyl-CoA
-
-
0.01
acetoacetyl-CoA
-
-
0.012
acetoacetyl-CoA
-
recombinant enzyme, hydrolase reaction
0.012
acetoacetyl-CoA
-
-
0.012
acetoacetyl-CoA
-
pH 7.5, 30C, mutant enzyme H188N
0.049
acetoacetyl-CoA
-
mutant D159A
0.058
acetoacetyl-CoA
-
mutant H264N
0.066
acetoacetyl-CoA
-
mutant D99A
0.115
acetoacetyl-CoA
-
mutant H264A
0.0015
acetyl-CoA
-
-
0.0078
acetyl-CoA
-
mutant D159A
0.0081
acetyl-CoA
-
mutant D159A, acetyl-S-enzyme formation
0.009
acetyl-CoA
-
absence of acetoacetyl-CoA, hydrolysis reaction
0.011
acetyl-CoA
-
acetyl-CoA hydrolysis, wild-type
0.014
acetyl-CoA
-
pH 8.0
0.014
acetyl-CoA
-
-
0.014
acetyl-CoA
-
wild-type, acetyl-CoA hydrolysis
0.014
acetyl-CoA
-
acetyl-CoA hydrolysis, mutant E95A
0.015
acetyl-CoA
-
acetyl-CoA hydrolysis
0.0152
acetyl-CoA
-
-
0.018
acetyl-CoA
-
pH 8.9
0.018
acetyl-CoA
-
-
0.018
acetyl-CoA
-
pH 7.5, 30C, mutant enzyme S89A
0.0227
acetyl-CoA
-
wild-type, acetyl-S-enzyme formation
0.024
acetyl-CoA
-
pH 7.5, 30C, mutant enzyme S359A
0.026
acetyl-CoA
-
pH 7.5, 30C, mutant enzyme S356A
0.027
acetyl-CoA
-
pH 7.5, 30C, mutant enzyme N115A
0.028
acetyl-CoA
-
mutant Y130F, hydrolysis partial reaction
0.029
acetyl-CoA
-
-
0.029
acetyl-CoA
-
pH 7.5, 30C, mutant enzyme C212S
0.033
acetyl-CoA
-
mutant D159A, acetyl-CoA hydrolysis
0.036
acetyl-CoA
-
mutant H264A, acetyl-CoA hydrolysis
0.037
acetyl-CoA
-
mutant D203A
0.038
acetyl-CoA
-
mutant H264N, acetyl-CoA hydrolysis
0.043
acetyl-CoA
-
pH 7.5, 30C, His6-BjHMGS1 wild-type enzyme
0.05
acetyl-CoA
-
0.005 mM acetoacetyl-CoA
0.05
acetyl-CoA
D4GWR6
pH 8.0, 30C
0.051
acetyl-CoA
-
-
0.052
acetyl-CoA
-
pH 7.5, 30C, mutant enzyme R157A
0.055
acetyl-CoA
-
pH 7.5, 30C, mutant enzyme H188N
0.073
acetyl-CoA
-
comparison of kinetic parameters measured in spectrophotometric cuvette and microplate format assays, DELTA A412 nm standard assay
0.076
acetyl-CoA
-
comparison of kinetic parameters measured in spectrophotometric cuvette and microplate format assays, DELTA A300 nm standard assay
0.084
acetyl-CoA
-
comparison of kinetic parameters measured in spectrophotometric cuvette and microplate format assays, DELTA A412 nm microplate assay
0.1
acetyl-CoA
-
-
0.118
acetyl-CoA
-
mutant D64N
0.12
acetyl-CoA
-
pH 7.5, 30C, mutant enzyme H188N/S359A
0.122
acetyl-CoA
-
mutant H264A
0.172
acetyl-CoA
-
mutant H264N
0.189
acetyl-CoA
-
mutant E63Q
0.2
acetyl-CoA
-
0.01 M acetoacetyl-CoA
0.2
acetyl-CoA
-
-
0.207
acetyl-CoA
-
mutant D99A
0.221
acetyl-CoA
-
mutant H436N
0.27
acetyl-CoA
-
reombinant enzyme
0.27
acetyl-CoA
-
-
0.274
acetyl-CoA
-
mutant C59A
0.28
acetyl-CoA
-
mutant C69A
0.29
acetyl-CoA
-
synthase I
0.29
acetyl-CoA
P23228
wild-type enzyme
0.294
acetyl-CoA
-
wild-type
0.294
acetyl-CoA
-
-
0.3
acetyl-CoA
-
0.1 mM acetoacetyl-CoA
0.3
acetyl-CoA
-
-
0.307
acetyl-CoA
-
mutant Y376F
0.31
acetyl-CoA
-
synthases II and III
0.319
acetyl-CoA
-
mutant D217A
0.35
acetyl-CoA
-
-
0.354
acetyl-CoA
-
mutant E37Q
0.355
acetyl-CoA
-
mutant C232A
0.358
acetyl-CoA
-
mutant D282A
0.372
acetyl-CoA
-
mutant E121A
0.4
acetyl-CoA
-
-
0.435
acetyl-CoA
-
mutant C268A
0.44
acetyl-CoA
-
mutant H197N
0.448
acetyl-CoA
-
mutant D203A, acetyl-S-enzyme formation
0.5
acetyl-CoA
-
0.05 mM acetoacetyl-CoA
0.53
acetyl-CoA
-
wild-type enzyme
0.565
acetyl-CoA
-
mutant Y130F
0.623
acetyl-CoA
-
mutant D99A, acetyl-S-enzyme formation
0.677
acetyl-CoA
-
mutant D124A
0.695
acetyl-CoA
-
-
0.811
acetyl-CoA
-
-
0.84
acetyl-CoA
-
mutant enzyme N326A
0.9
acetyl-CoA
-
mutant enzyme C117A
1
acetyl-CoA
-
mitochondrial synthase
1.561
acetyl-CoA
-
mutant C224A
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0017
acetyl-CoA
-
pH 7.5, 30C, mutant enzyme R157A
0.0029
acetyl-CoA
-
pH 7.5, 30C, mutant enzyme H188N
0.0041
acetyl-CoA
-
pH 7.5, 30C, mutant enzyme C212S
0.0076
acetyl-CoA
-
pH 7.5, 30C, mutant enzyme S89A
0.0161
acetyl-CoA
-
pH 7.5, 30C, mutant enzyme S356A
0.0234
acetyl-CoA
-
pH 7.5, 30C, mutant enzyme N115A
0.0417
acetyl-CoA
-
-
0.0667
acetyl-CoA
-
-
0.214
acetyl-CoA
-
pH 7.5, 30C, mutant enzyme S359A
0.415
acetyl-CoA
-
pH 7.5, 30C, His6-BjHMGS1 wild-type enzyme
4.6
acetyl-CoA
D4GWR6
pH 8.0, 30C
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
92
acetyl-CoA
D4GWR6
pH 8.0, 30C
29
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.009
(S)-3-hydroxy-3-methylglutaryl-CoA
-
pH 7.5, 30C, wild-type enzyme
0.034
(S)-3-hydroxy-3-methylglutaryl-CoA
-
pH 7.5, 30C, mutant enzyme H188N
0.0389
(S)-3-hydroxy-3-methylglutaryl-CoA
-
pH 7.5, 30C, mutant enzyme H188N/S359A
0.12
3,3'-dimethylglutaryl-CoA
-
pH 8.0
-
0.015
3-Chloropropionyl-CoA
-
-
0.0011
3-hydroxy-3-methylglutaryl-CoA
-
comparison of kinetic parameters measured in spectrophotometric cuvette and microplate format assays, DELTA A300 nm standard assay
0.0015
3-hydroxy-3-methylglutaryl-CoA
-
comparison of kinetic parameters measured in spectrophotometric cuvette and microplate format assays, DELTA A412 nm standard assay
0.0031
3-hydroxy-3-methylglutaryl-CoA
-
comparison of kinetic parameters measured in spectrophotometric cuvette and microplate format assays, DELTA A412 nm microplate assay
0.0071
3-Oxohexanoyl-CoA
-
pH 8.0
0.014
3-Oxohexanoyl-CoA
-
pH 8.0, mixed inhibition, substrate acetoacetyl-CoA
0.00126
acetoacetyl-CoA
-
-
0.0035
acetoacetyl-CoA
-
-
0.006 - 0.01
acetoacetyl-CoA
-
-
0.008
acetoacetyl-CoA
-
pH 8.0
0.008
acetoacetyl-CoA
-
-
0.01
acetoacetyl-CoA
-
-
0.012
acetoacetyl-CoA
-
-
0.012
acetoacetyl-CoA
-
-
0.02
acetoacetyl-CoA
-
pH 8.9
0.028
acetoacetyl-CoA
-
pH 7.5, 30C, mutant enzyme S359A
0.038
acetoacetyl-CoA
-
pH 7.5, 30C, wild-type enzyme
0.039
acetoacetyl-CoA
-
pH 7.5, 30C, mutant enzyme C212S
0.046
acetoacetyl-CoA
-
pH 7.5, 30C, mutant enzyme S89A
0.091
acetoacetyl-CoA
-
pH 7.5, 30C, mutant enzyme N115A
0.199
acetoacetyl-CoA
-
pH 7.5, 30C, mutant enzyme S356A
0.242
acetoacetyl-CoA
-
pH 7.5, 30C, mutant enzyme R157A
0.033
Butyryl-CoA
-
pH 8.0
0.038
CoA
-
pH 8.0, mixed inhibition, substrate acetyl-CoA
0.06
CoA
-
pH 8.0, mixed inhibition, substrate acetoacetyl-CoA
0.08
CoA
-
pH 7.5, 30C, wild-type enzyme
0.0027
decanoyl-CoA
-
pH 8.0
0.03
desulfo-CoA
-
pH 8.0
0.07
desulfo-CoA
-
pH 8.0, mixed inhibition, substrate acetoacetyl-CoA
0.012
DL-3-hydroxy-3-methylglutaryl-CoA
-
-
0.013
DL-3-hydroxy-3-methylglutaryl-CoA
-
pH 8.0, competitive inhibition, substrate acetyl-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
hymeglusin
D4GWR6
18C, pH 8
0.7
hymeglusin
Q9FD71
in 100 mM Tris-HCl (pH 8.0), at 18C
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
LITERATURE
IMAGE
0.000035
F-244
-
IC50: 35 nM
0.00032
hymeglusin
-
IC50: 0.00032 mM, inhibitor binds to the thiol residue of Cys
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
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
P54869
activity in response to acetaminophen, APAP, treatment
0.057
P54869
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
LITERATURE
8
-
activity assay
8
D4GWR6
assay at
8.2
P54869
activity assay
8.5
D4GWR6
-
9.2
-
synthase II
9.3
-
synthase I
9.4
-
synthase III
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
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
-
-
8 - 9.6
-
-
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
24
-
activity assay, A412 nm assay
30
-
activity assay, A300 nm assay
30
P54869
activity assay
30
D4GWR6
assay at
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
30 - 45
-
about 70% of maximal activity at 30C and at 45C
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
synthases I, II and III
Manually annotated by BRENDA team
-
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
-
expression of BjHMGS1 and BjHMGS2. No expression of BjHMGS3 and BjHMGS4
Manually annotated by BRENDA team
Brassica juncea BjHMGS2, Brassica juncea BjHMGS3, Brassica juncea BjHMGS1, Brassica juncea BjHMGS4
-
expression of BjHMGS1 and BjHMGS2. No expression of BjHMGS3 and BjHMGS4
-
Manually annotated by BRENDA team
-
HMGS2 is well expressed
Manually annotated by BRENDA team
-
HMGS2 is poorly expressed
Manually annotated by BRENDA team
-
of adults
Manually annotated by BRENDA team
-
hepatic mRNA expression of 3-hydroxyl-3-methyl-glutaryl-CoA synthase is significantly decreased (27%) in the liver of gallstone patients compared with gallstone-free patients
Manually annotated by BRENDA team
Rattus norvegicus Sprague-Dawley
-
-
-
Manually annotated by BRENDA team
Rattus norvegicus Sprague-Dawley
-
-
-
Manually annotated by BRENDA team
-
HMGS2 is well expressed
Manually annotated by BRENDA team
-
developmental regulation
Manually annotated by BRENDA team
-
developmental regulation. Expression is highest in young hypocotyls and is induced during the greening of etiolated cotyledons
Manually annotated by BRENDA team
-
mRNA levels in newborn rats is low, when suckling begins, there is a net increase in gene expression up to day 12, levels then plateau until day 15, and then decreases progressively throughout the suckling period, becoming zero after weaning (day 21) and remains so in the adult rat
Manually annotated by BRENDA team
Q5EE42
anterior midgut, topically applied juvenile hormone III induced enzyme mRNA levels up to 6.5fold
Manually annotated by BRENDA team
additional information
-
in flower bud expression of BjHMGS1 and BjHMGS2, no expression of BjHMGS3 and BjHMGS4
Manually annotated by BRENDA team
additional information
-
no expressed in small intestine, stomach, kidney, ovary or testis
Manually annotated by BRENDA team
additional information
Brassica juncea BjHMGS2, Brassica juncea BjHMGS3, Brassica juncea BjHMGS1, Brassica juncea BjHMGS4
-
in flower bud expression of BjHMGS1 and BjHMGS2, no expression of BjHMGS3 and BjHMGS4
-
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
cholesterogenic isoform
Manually annotated by BRENDA team
Q01581
cholesterogenic isoform
Manually annotated by BRENDA team
P54871
cholesterogenic isoform
Manually annotated by BRENDA team
-
cholesterogenic isoform
Manually annotated by BRENDA team
P17425
cholesterogenic isoform
Manually annotated by BRENDA team
-
distinct mitochondrial and cytoplasmic forms
Manually annotated by BRENDA team
Rattus norvegicus Sprague-Dawley
-
-
-
Manually annotated by BRENDA team
-
cholesterogenic isoform
Manually annotated by BRENDA team
Q01581
cholesterogenic isoform
Manually annotated by BRENDA team
P54871
cholesterogenic isoform
Manually annotated by BRENDA team
-
cholesterogenic isoform
Manually annotated by BRENDA team
P17425
cholesterogenic isoform
Manually annotated by BRENDA team
-
cholesterogenic isoform
Manually annotated by BRENDA team
P54868, Q01581
isoform HMGCS1
Manually annotated by BRENDA team
Brassica juncea BjHMGS2, Brassica juncea BjHMGS3, Brassica juncea BjHMGS1, Brassica juncea BjHMGS4
-
BjHMGS1
-
Manually annotated by BRENDA team
-
distinct mitochondrial and cytoplasmic forms
Manually annotated by BRENDA team
-
ketogenic isoform
Manually annotated by BRENDA team
Q01581
ketogenic isoform
Manually annotated by BRENDA team
P54871
ketogenic isoform
Manually annotated by BRENDA team
P17425
ketogenic isoform
Manually annotated by BRENDA team
P54868, Q01581
isoform HMGCS2
Manually annotated by BRENDA team
Rattus norvegicus Sprague-Dawley
-
-
-
Manually annotated by BRENDA team
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
50000
-
SDS-PAGE, immunoblot by antibodies, prediction from cDNA nucleotide sequence
488116
50000
-
recombinant enzyme, epressed in Mev-1 cells
488120
51040
-
predicted from cDNA sequence
488113
53000
-
SDS-PAGE
488114
55500
-
SDS-PAGE
488113
56000
-
recombinant enzyme, epressed in Escherichia coli
488120
56800
P54869
determined by MALDI-TOF mass spectrometry
706833
57250
-
deduced amino acid sequence
488113
57290
-
deduced amino acid sequence
488113
57370
-
deduced amino acid sequence
488113
57490
-
deduced amino acid sequence
488113
57600
-
SDS-PAGE
488110
83900
-
analytical ultracentrifugation
488122
84300
-
calculated from amino acid sequence
488122
88000
-
gel filtration
488101
90000
-
gel filtration, synthase I
488096
94000 - 100000
-
gel filtration, synthase II
488096
94600
-
sedimentation equilibrium
488103
96000 - 105000
-
gel filtration, mitochondrial synthase
488096
96000
-
gel filtration
488099
100000
-
cytosolic enzyme, sedimentation equilibrium
488095
100000
-
gel filtration, synthases I, II, III, IV, multiple forms of cytoplasmic enzyme
488096
100000
-
-
488103
105000
-
sedimentation equlibrium
488098, 488099, 488100, 488107
111000
-
gel filtration
488103
116000
-
gel filtration
488118
119300
-
sedimentation velocity and light-scattering
488103
120000
-
gel filtration
488111
130000
-
gel filtration
488092, 488097
130000
-
-
488103
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
?
D4GWR6
x * 65000, SDS-PAGE, x * 51975, matrix-assisted laser desorption ionization-time of flight mass spectrometry
?
Haloferax volcanii DSM 3757
-
x * 65000, SDS-PAGE, x * 51975, matrix-assisted laser desorption ionization-time of flight mass spectrometry
-
dimer
-
-
dimer
-
2 * 45000, SDS-PAGE
dimer
-
2 * 53000, SDS-PAGE
dimer
-
2 * 53000, SDS-PAGE
dimer
-
2 * 42000, calculated from amino acid sequence
dimer
-
2 * 52000, mitochondrial synthase, synthase I, SDS-PAGE
dimer
-
2 * 55000, synthase II, SDS-PAGE
dimer
-
2 * 47900, SDS-PAGE
dimer
-
2 * 58000, synthases III and IV, SDS-PAGE
dimer
-
2 * 57600
dimer
-
2 * 57000, gel filtration
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
bound covalently via Cys 117 to inhibitor (E,E)-11-(3-hydroxymethyl-4-oxo-2-oxytanyl)-3,5,7-trimethyl-2,4-undecadienoic acid, and in complex with acetyl-CoA and hydroxymethylglutaryl-CoA
-
in complex with hymeglusin, hanging drop vapor diffusion method, using 0.1 M Bis-Tris (pH 6.3-6.5), 0.2 M NaCl, and 23% (w/v) polyethylene glycol 3350
Q9FD71
mutant A110G. Amide nitrogen of mutants S308 shifts 0.4 A toward the catalytic site cysteine residue stabilizing the intermediate negative charge. The hydroxyl group of S308 rotates to a position where it is able to stabilize the carbanion intermediate of the acetyl-S-enzyme during its condensation with acetoacetyl-CoA
-
unliganded and in complex with its second substrate/inhibitor acetoacetyl-CoA. The acetoacetyl-CoA binary structure demonstrates reduced coenzyme A and acetoacetate covalently bound to the active site cysteine through a thioester bond
-
in complex with Co-A, sitting drop vapor diffusion method, using 0.1 M Bis-Tris (pH 6.5), 25% (w/v) polyethylene glycol (PEG) 3350, 0.2 M ammonium sulfate, at 4C; in complex with (S)-3-hydroxy-3-methylglutaryl-CoA, sitting drop vapor diffusion method, using 0.2 M ammonium sulfate, 0.1 M Bis-Tris (pH 6.5), 25% (w/v) PEG 3350, at 20C
P54868, Q01581
sitting-drop vapour-diffusion method, crystal strcuture of full-length enzyme expressed in Escherichia coli is determined at 2.0 A resolution, crystal structure of HMG-CoA synthase with acetoacetyl-CoA is determined at 2.5 A resolution
-
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
45
D4GWR6
in the presence of an excess of acetyl-CoA, the half-life of the active enzyme is 27 h
727772
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
can be rapidly frozen in solid CO2/acetone and freeze-dried for long-term storage, not stable to freezing and thawing in absence of glycerol
-
enzyme is vulnerable to proteolysis, expression in Escherichia coli leads to an quite stable enzyme
-
relatively stable dialyzed against 10 mM potassium phosphate in 0.1 mM dithiothreitol and EDTA for 4-10 days
-
enzyme is labile to freezing and thawing, stabilized by glycerol
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-20C, stored in presence of 30% glycerol and 5 mM dithiothreitol, remains active for several months
-
-20C, may be stored in 30% glycerin solution for 2-3 months with no loss of activity
-
-20C, purified synthase may be stored for 2-3 months with little loss of activity by adding 30% glyerol
-
-80C, recombinant enzyme, negligible loss of activity after 1 year
-
-85C, in presence of 30% glycerol stable for over 1 year
-
-90C, purified synthases II-IV in 20 mM potassium phosphate, pH 7.0, 5 mM dithiothreitol, can be stored as pellets following precipitation by 60% saturated ammonium sulfate up to 3 months without loss of activity
-
0C, purified synthase I stored frozen in 40% glycerol containing 20 mM potassium phosphate, pH 7.0, 5 mM dithiothreitol, stable for 3-4 months
-
4C, in presence of 30% glycerol stable for several days
-
4C, purified synthase I stored in 40% glycerol containing 20 mM potassium phosphate, pH 7.0, 5 mM dithiothreitol is unstable
-
4C, purified synthases II-IV in 20 mM potassium phosphate, pH 7.0, 5 mM dithiothreitol, stable for several weeks
-
4C, recombinant enzyme, loses 50% activity after 1 year
-
-20, stored in presence of dithiothreitol and 30-50% glycerol purified enzyme retains complete activity for up to 3 months
-
4C, enzyme loses activity in absence of glycerol
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
recombinant enzyme
-
recombinant
-
Ni2+-NTA Sepharose column chromatography and Resource Q anion-exchange column chromatography
Q9FD71
recombinant enzyme
-
cytosolic synthase
-
mitochondrial form
-
partially
-
recombinant enzyme, expressed in Escherichia coli
-
several mutants partially purified
-
synthase species I-IV
-
Ni-Sepharose resin column chromatography and Superdex 200 gel filtration; Ni-Sepharose resin column chromatography and Superdex 200 gel filtration
P54868, Q01581
mitochondria are prepared
P54869
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
cDNA cloned by complementation of a bap1 mutation and expressed in Saccharomyces cerevisiae
-
2 cytosolic HMG-CoA synthase genes, HMGS-1 and HMGs-2 described, HMGS-1 cloned in expression vector pSBLA1 and overexpressed in Escherichia coli BL21DE3 pLys S; intronless gene, encodes for an active enzyme able to complement eukaryotic Mev-1 cells
-
intronless gene, encodes for an active enzyme able to complement eukaryotic Mev-1 cells
-
expressed in Arabidopsis thaliana
-
expression in Escherichia coli
-
His6-tagged protein from Escherichia coli,His6-BjHMGS1
-
expression in Escherichia coli
-
expressed in Escherichia coli BL21(DE3) cells
Q9FD71
mvaS gene isolated, expressed in Escherichia coli from a pET28 vector
-
cDNA cloned and sequenced
-
expression vector pET-3d, cloned and expressed in Escherichia coli BL21 (DE3)
-
expression in Haloferax volcanii
D4GWR6
; HMGS1, expression in Escherichia coli
-
cDNA cloned and sequenced
-
cDNA subcloned and expressed from a T7-based vector in Escherichia coli
-
expressed in Escherichia coli BL21(DE3) cells; expressed in Escherichia coli BL21(DE3) cells
P54868, Q01581
expressed in Escherichia coli BL21-Codon Plus (DE3)-RIPL cells
-
expression of recombinant wild-type cytoplasmic and Cys129 mutant enzymes
-
into the vector pET-HSyn for expression in Escherichia coli cells
-
-
Q5EE42
cDNA cloned and sequenced
-
rat mitochondrial HMG-CoA synthase encodes an active enzyme in the eukaryotic cell line Mev-1 in Escherichia coli BL21 (DE3)
-
expression in Escherichia coli
-
cloning of a gene cluster encoding enzymes responsible for the mevalonate pathway
-
pig mitochondrial HMG-CoA synthase encodes an active enzyme in the eukaryotic cell line Mev-1 and in Escherichia coli BL21 (DE3)
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
3-hydroxy-3-methylglutaryl-CoA synthase 2 has significantly decreased levels of reduced thiols and activity after acetaminophen treatment
P54869
lower renal expression of HMGCS2 in SHRSPs than in SHRs or clofibrate-treated SHRSPs
P22791
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
C212C
-
mutation causes 6fold decreased maximal velocity
H188N
-
mutation causes 8fold decreased maximal velocity, mutant enzyme does not display substrate inhibition by acetoacetyl-CoA
H188N
-
the mutant lacks substrate inhibition by acetoacetyl-CoA and shows 8fold decreased enzyme activity
H188N/S359A
-
10fold increased specific activity, no inhibition by acetoacetyl-CoA
H188N/S359A
-
the double mutant displays a 10fold increased enzyme activity and lacks inhibition by acetoacetyl-CoA
N115A
-
KI value for acetoacetyl-CoA is 2.3fold higher than the wild-type value, the turnover number for acetyl-CoA is 17.7fold lower than wild-type value, KM-value is 1.6fold lower than wild-type value
R157A
-
mutation causes 14fold decreased maximal velocity
S356A
-
KI value for acetoacetyl-CoA is 5.2fold higher than the wild-type value, the turnover number for acetyl-CoA is 25.8fold lower than wild-type value, KM-value is 1.6fold lower than wild-type value
S359A
-
10fold increased specific activity
S359A
-
the mutant demonstrates 10fold higher activity as the wild type enzyme
S89A
-
KI value for acetoacetyl-CoA is 1.2fold higher than the wild-type value, the turnover number for acetyl-CoA is 54.6fold lower than wild-type value, KM-value is 2.3fold lower than wild-type value
A110G
-
overall reaction rate increases 140fold due to adjustments in the active site that result in additional stabilization of all three steps of the reaction pathway. Crystallization data
C117A
-
Km-value for acetyl-CoA is 1.7fold higher than the wild-type value, specific activity is 30% of wild-type activity
N326A
-
Km-value for acetyl-CoA is 1.6fold higher than the wild-type value, specific activity is 5% of wild-type activity
F174L
P54868, Q01581
the mutant shows 10000fold decrease of activity compared to the wild type enzyme
G169D
P54868, Q01581
the mutant is associated with HMGCS2 deficiency
G212R
P54868, Q01581
inactive
G388R
P54868, Q01581
the mutant is associated with HMGCS2 deficiency
I407T
P54868, Q01581
the mutant is associated with HMGCS2 deficiency
I56N
P54868, Q01581
the mutant is associated with HMGCS2 deficiency
K243E
P54868, Q01581
the mutant is associated with HMGCS2 deficiency
L266S
P54868, Q01581
the mutant is associated with HMGCS2 deficiency
M307T
P54868, Q01581
the mutant is associated with HMGCS2 deficiency
R188H
P54868, Q01581
the mutant is associated with HMGCS2 deficiency
R424X
P54868, Q01581
the truncated mutant is nonfunctional
R500H
P54868, Q01581
inactive
R505Q
P54868, Q01581
the mutant is associated with HMGCS2 deficiency
T233A
P54868, Q01581
the mutant is associated with HMGCS2 deficiency
V54M
P54868, Q01581
the mutant is associated with HMGCS2 deficiency
Y167C
P54868, Q01581
the mutant is associated with HMGCS2 deficiency
Y84X
P54868, Q01581
the truncated mutant is nonfunctional
additional information
-
construction of a double mutant by deletion of genes involved in leucine degradation and disruption of hydroxymethylglutaryl-Coa synthase gene. For the mutant, a dramatic decrease is observed of isovaleryl-CoA derived iso-odd fatty acids
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
synthesis
-
use of crystal structure of enzyme in complex with inhibitor (E,E)-11-(3-hydroxymethyl-4-oxo-2-oxytanyl)-3,5,7-trimethyl-2,4-undecadienoic acid as starting point for structure-based design of inhibitors
medicine
-
potential of the mevalonate pathway enzymes of enterococci as targets for antibiotics
analysis
-
a visible wavelength spectrophotometric assay suitable for high-throughput screening of 3-hydroxy-3-methylglutaryl-CoA synthase is established
medicine
-
-
medicine
-
target of a potent antisteroidogenic drug
medicine
-
enzyme is of growing medical interest as it is highly regulated
medicine
-
deficiency of the mitochondrial isoform correlates with human metabolic disease, cytosolic isoform is potentially useful target for drugs aimed at lowering cholesterol levels
medicine
-
expression of isoform HMGCS2 is down-regulated in 90% of Myc-dependent colon and rectum tumors. Protein expression is down-regulated preferentially in moderately and poorly differentiated carcinomas. In addition, it is also down-regulated in 80% of small intestine Myc-independent tumors
medicine
P54869
acetaminophen, APAP, is a leading cause of drug-induced liver failure