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Information on EC 1.1.1.34 - hydroxymethylglutaryl-CoA reductase (NADPH) and Organism(s) Saccharomyces cerevisiae and UniProt Accession P12683
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1.1.1.34 hydroxymethylglutaryl-CoA reductase (NADPH)IUBMB Comments
The enzyme is inactivated by EC 2.7.11.31 {[hydroxymethylglutaryl-CoA reductase (NADPH)] kinase} and reactivated by EC 3.1.3.47 {[hydroxymethylglutaryl-CoA reductase (NADPH)]-phosphatase}.
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Word Map
- 1.1.1.34
- cholesterol
- statin
- lipoprotein
- simvastatin
- sterol
- cardiovascular
- triglyceride
-
low-density
- hypercholesterolemia
- lovastatin
- pravastatin
- coronary
-
lipid-lowering
- bile
- endothelial
- artery
- atorvastatin
- atherosclerosis
-
isoprenoids
- hdl
-
cholesterol-lowering
- hyperlipidemia
-
ldl-cholesterol
-
placebo
- squalene
-
apolipoproteins
- myopathy
-
hypocholesterolemic
-
farnesylation
-
geranylgeranylation
-
hypolipidemic
- rosuvastatin
- dyslipidemias
-
high-density
-
fibrates
- cyp7a1
- cholestyramine
- rhabdomyolysis
-
7alpha-hydroxylase
- drug development
- medicine
- nutrition
-
acyl-coa:cholesterol
- molecular biology
- 25-hydroxycholesterol
- lanosterol
- gemfibrozil
- pcsk9
- ezetimibe
- biotechnology
- dolichols
-
isoprenylation
- srebp-2
-
statin-induced
-
lipoprotein-cholesterol
The taxonomic range for the selected organisms is: Saccharomyces cerevisiae
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Reaction Schemes
+
+
2
=
+
2
+
2
Synonyms
hmg-coa reductase, hmgcr, 3-hydroxy-3-methylglutaryl coenzyme a reductase, hmgr, hmg coa reductase, 3-hydroxy-3-methylglutaryl-coa reductase, 3-hydroxy-3-methylglutaryl-coenzyme a reductase, hmgcoa reductase, 3-hydroxy-3-methylglutaryl coa reductase, hmg-coar, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
3-hydroxy-3-methylglutaryl-CoA reductase
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-
-
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3-hydroxy-3-methylglutaryl-CoA reductase (NADPH)
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-
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beta-hydroxy-beta-methylglutaryl coenzyme A reductase
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-
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beta-hydroxy-beta-methylglutaryl-Co A reductase
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-
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HMG-CoA reductase
HMG2.2
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-
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HMG3.3
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-
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HMGCoA reductase-mevalonate:NADP-oxidoreductase (acetylating CoA)
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-
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HMGR
HMGR1
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-
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HMGR2
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-
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hydroxymethylglutaryl CoA reductase (NADPH)
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hydroxymethylglutaryl-coenzyme A reductase (reduced nicotinamide adenine dinucleotide phosphate)
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mevalonate:NADP+ oxidoreductase (acetylating CoA)
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-
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NADPH-hydroxymethylglutaryl-CoA reductase
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-
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S-3-hydroxy-3-methylglutaryl-CoA reductase
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-
-
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HMG-CoA reductase
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-
-
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HMGR
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-
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-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
redox reaction
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-
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oxidation
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-
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reduction
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PATHWAY SOURCE
PATHWAYS
BRENDA
-
-, -, -, -, -
SYSTEMATIC NAME
IUBMB Comments
(R)-mevalonate:NADP+ oxidoreductase (CoA-acylating)
The enzyme is inactivated by EC 2.7.11.31 {[hydroxymethylglutaryl-CoA reductase (NADPH)] kinase} and reactivated by EC 3.1.3.47 {[hydroxymethylglutaryl-CoA reductase (NADPH)]-phosphatase}.
CAS REGISTRY NUMBER
COMMENTARY
9028-35-7
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
D-3-hydroxy-3-methylglutaryl-CoA + NADPH
mevalonate + CoA + NADP+
-
-
-
-
?
3-hydroxy-3-methylglutaryl-CoA + NADPH
(R)-mevalonate + CoA + NADP+
-
-
-
-
?
3-hydroxy-3-methylglutaryl-CoA + NADPH
(R)-mevalonate + CoA + NADP+
-
-
-
-
ir
additional information
?
-
enzyme in the pathway for production of prenyl alcohols. Almost all Saccharomyces cerevisiae strains tend to produce mainly squalene and low amount of prenyl alcohols. Among these ATCC strains, relatively large amounts of prenyl alcohols in the cultures of two recombinants (ATCC201741 and ATCC 200027). Amounts are quite low compared to the case of ATCC 200589 recombinant. These differences possibly depend on the difference in the squalene synthase activity. If the enzyme activity is weaker in ATCC 200589, the activation of the pathways will result in the accumulation of (E,E)-farnesyl diphosphate, the substrate of the enzyme, and following production of (E,E)-farnesol through hydrolysis of (E,E)-farnesyl diphosphate. Recombinant AURGG101 derived from ATCC 200589 produces large amounts of prenyl alcohols. In particular, (E,E)-farnesol in AURGG101 reaches 35.6 mg/l, which is approximately 4fold higher than that in ATCC 200589. HMG1 expression in strain ATCC 200589 increases the production of squalene, (E)-nerolidol, (E,E)-farnesol, and (E,E,E)-geranylgeraniol, whereas that in ATCC 76625 causes high squalene production, low production of (E,E)-farnesol and (E,E,E)-geranylgeraniol, and no (E)-nerolidol production
-
-
?
additional information
?
-
-
enzyme in the pathway for production of prenyl alcohols. Almost all Saccharomyces cerevisiae strains tend to produce mainly squalene and low amount of prenyl alcohols. Among these ATCC strains, relatively large amounts of prenyl alcohols in the cultures of two recombinants (ATCC201741 and ATCC 200027). Amounts are quite low compared to the case of ATCC 200589 recombinant. These differences possibly depend on the difference in the squalene synthase activity. If the enzyme activity is weaker in ATCC 200589, the activation of the pathways will result in the accumulation of (E,E)-farnesyl diphosphate, the substrate of the enzyme, and following production of (E,E)-farnesol through hydrolysis of (E,E)-farnesyl diphosphate. Recombinant AURGG101 derived from ATCC 200589 produces large amounts of prenyl alcohols. In particular, (E,E)-farnesol in AURGG101 reaches 35.6 mg/l, which is approximately 4fold higher than that in ATCC 200589. HMG1 expression in strain ATCC 200589 increases the production of squalene, (E)-nerolidol, (E,E)-farnesol, and (E,E,E)-geranylgeraniol, whereas that in ATCC 76625 causes high squalene production, low production of (E,E)-farnesol and (E,E,E)-geranylgeraniol, and no (E)-nerolidol production
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-
?
additional information
?
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-
enzyme undergoes endoplasmic reticulum-associated degradation which is physiologically regulated by sterol pathway signals, determination of structural features leading to modification and degradation by the quality control system of the endoplasmic reticulum, overview
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-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
D-3-hydroxy-3-methylglutaryl-CoA + NADPH
mevalonate + CoA + NADP+
-
-
-
-
?
additional information
?
-
-
enzyme undergoes endoplasmic reticulum-associated degradation which is physiologically regulated by sterol pathway signals, determination of structural features leading to modification and degradation by the quality control system of the endoplasmic reticulum, overview
-
-
?
3-hydroxy-3-methylglutaryl-CoA + NADPH
(R)-mevalonate + CoA + NADP+
-
-
-
-
?
3-hydroxy-3-methylglutaryl-CoA + NADPH
(R)-mevalonate + CoA + NADP+
-
-
-
-
ir
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
NaCl
-
specific HMGR activity is responsive to changes in NaCl concentrations. Minimal activity under optimal conditions and an increase in HMGR activities and protein levels under hyposaline and hypersaline conditions. HMGR activity is crucial for halotolerance as well as for the changes in protein prenylation in response to changing salinity
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
CoA disulfide
-
no inactivation in presence of NADPH 1 mM, or HMG-CoA 0.5 mM
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
additional information
-
enzyme undergoes endoplasmic reticulum-associated degradation which is physiologically regulated by sterol pathway signals
-
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
glycerol strongly stabilizes the enzyme, stabilization against endoplasmic reticulum-associated degradation
-
ORGANIC SOLVENT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dithiothreitol
-
10 mM at pH 7 reverses CoA disulfide inactivation of enzyme
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
partially, preparation of microsomes and solubilization by trypsin
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
the HMG1-overexpressing episome (pRS434GAP-HMG1) introduced into 36 type strains purchased from ATCC, and yeast recombinant AURGG101
expression of c-myc-tagged enzyme from plasmid in yeast, expression as GFP-fusion protein
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
biotechnology
overexpression of HMG1 is the most effective among all other genes in both hosts Saccharomyces cerevisiae ATCC 200589 and ATCC 76625 for prenyl alcohol production
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Durr, I.F.; Rudney, H.
The reduction of beta-hydroxy-beta-methylglutaryl coenzyme A to mevalonic acid
J. Biol. Chem.
235
2572-2578
1960
Saccharomyces cerevisiae
Madhosingh, C.; Migicovski, B.B.; Wood, I.M.
Inhibition of yeast hydroxymethylglutaryl-CoA reductase by a rat liver mitochondrial preperation
FEBS Lett.
46
20-22
1974
Saccharomyces cerevisiae, Rattus norvegicus
Gilbert, H.F.; Stewart, M.D.
Inactivation of hydroxymethylglutaryl-CoA reductase from yeast by coenzyme A disulfide
J. Biol. Chem.
256
1782-1785
1981
Saccharomyces cerevisiae
Shearer, A.G.; Hampton, R.Y.
Structural control of endoplasmic reticulum-associated degradation: effect of chemical chaperones on 3-hydroxy-3-methylglutaryl-CoA reductase
J. Biol. Chem.
279
188-196
2004
Saccharomyces cerevisiae
Ohto, C.; Muramatsu, M.; Obata, S.; Sakuradani, E.; Shimizu, S.
Overexpression of the gene encoding HMG-CoA reductase in Saccharomyces cerevisiae for production of prenyl alcohols
Appl. Microbiol. Biotechnol.
82
837-845
2009
Saccharomyces cerevisiae (P12683), Saccharomyces cerevisiae
Vaupotic, T.; Veranic, P.; Petrovic, U.; Gunde-Cimerman, N.; Plemenitas, A.
HMG-CoA reductase is regulated by environmental salinity and its activity is essential for halotolerance in halophilic fungi
Stud. Mycol.
61
61-66
2008
Aspergillus amstelodami, Aureobasidium pullulans, Saccharomyces cerevisiae, Debaryomyces hansenii, Hortaea werneckii, Neophaeotheca triangularis, Trimmatostroma salinum, Wallemia ichthyophaga, Saccharomyces cerevisiae MZKI K86, Wallemia ichthyophaga EXF 994, Neophaeotheca triangularis MZKI B741, Aureobasidium pullulans MZKI B802, Hortaea werneckii MZKI B736, Aspergillus amstelodami MZKI A561, Debaryomyces hansenii CBS 767, Trimmatostroma salinum MZKI B734
EXTERNAL LINKS (specific for EC-Number 1.1.1.34)
Transporter Classification Database (TCDB): 2.A.6.6.5, 2.A.6.6.10
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