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Showing metabocard for 3-Hydroxy-3-methylglutaryl-CoA (HMDB0001375)

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IdentificationTaxonomyOntologyPhysical propertiesSpectraBiological propertiesConcentrationsLinksReferencesenzymes (6) Show 6 proteinsXML
enzymes (6) Show 6 proteins
Record Information
Version4.0
StatusExpected but not Quantified
Creation Date2005-11-16 15:48:42 UTC
Update Date2020-06-15 17:04:52 UTC
HMDB IDHMDB0001375
Secondary Accession Numbers
  • HMDB01375
Metabolite Identification
Common Name3-Hydroxy-3-methylglutaryl-CoA
Description3-Hydroxy-3-methylglutaryl-CoA (HMG-CoA) (CAS: 1553-55-5) is formed when acetyl-CoA condenses with acetoacetyl-CoA in a reaction that is catalyzed by the enzyme HMG-CoA synthase in the mevalonate pathway or mevalonate-dependent (MAD) route, an important cellular metabolic pathway present in virtually all organisms. HMG-CoA reductase (EC 1.1.1.34) inhibitors, more commonly known as statins, are cholesterol-lowering drugs that have been widely used for many years to reduce the incidence of adverse cardiovascular events. HMG-CoA reductase catalyzes the rate-limiting step in the mevalonate pathway and these agents lower cholesterol by inhibiting its synthesis in the liver and in peripheral tissues. Androgen also stimulates lipogenesis in human prostate cancer cells directly by increasing transcription of the fatty acid synthase and HMG-CoA-reductase genes (PMID: 14689582 ).
Structure
Data?1583445288
MOLSDFPDBSMILESInChI
Synonyms
ValueSource
(3S)-3-Hydroxy-3-methylglutaryl-coenzyme AChEBI
(S)-3-Hydroxy-3-methylglutaryl-coenzyme AChEBI
3-Hydroxy-3-methylglutaryl-CoAChEBI
HMG-CoAChEBI
HMG-coenzyme AChEBI
Hydroxymethylglutaroyl coenzyme AChEBI
Hydroxymethylglutaryl-CoAChEBI
(3S)-3-Hydroxy-3-methylglutaryl-CoAHMDB
(S)-3-Hydroxy-3-methylglutaryl coenzyme AHMDB
(S)-3-Hydroxy-3-methylglutaryl-CoAHMDB
3-Hydroxy-3-methylglutaryl CoAHMDB
3-Hydroxy-3-methylglutaryl coenzyme AHMDB
Hydroxymethylglutaryl CoAHMDB
Hydroxymethylglutaryl coenzyme AHMDB
beta-Hydroxy-beta-methylglutaryl CoAHMDB
beta-Hydroxy-beta-methylglutaryl-CoAHMDB
beta-Hydroxy-beta-methylglutaryl-coenzyme AHMDB
β-Hydroxy-β-methylglutaryl CoAHMDB
β-Hydroxy-β-methylglutaryl-CoAHMDB
β-Hydroxy-β-methylglutaryl-coenzyme AHMDB
Chemical FormulaC27H44N7O20P3S
Average Molecular Weight911.659
Monoisotopic Molecular Weight911.157467109
IUPAC Name(3S)-5-[(2-{3-[(2R)-3-[({[({[(2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-4-hydroxy-3-(phosphonooxy)oxolan-2-yl]methoxy}(hydroxy)phosphoryl)oxy](hydroxy)phosphoryl}oxy)methyl]-2-hydroxy-3-methylbutanamido]propanamido}ethyl)sulfanyl]-3-hydroxy-3-methyl-5-oxopentanoic acid
Traditional NameHMG-CoA
CAS Registry Number26926-09-0
SMILES
C[C@](O)(CC(O)=O)CC(=O)SCCNC(=O)CCNC(=O)[C@H](O)C(C)(C)COP(O)(=O)OP(O)(=O)OC[C@H]1O[C@H]([C@H](O)[C@@H]1OP(O)(O)=O)N1C=NC2=C1N=CN=C2N
InChI Identifier
InChI=1S/C27H44N7O20P3S/c1-26(2,21(40)24(41)30-5-4-15(35)29-6-7-58-17(38)9-27(3,42)8-16(36)37)11-51-57(48,49)54-56(46,47)50-10-14-20(53-55(43,44)45)19(39)25(52-14)34-13-33-18-22(28)31-12-32-23(18)34/h12-14,19-21,25,39-40,42H,4-11H2,1-3H3,(H,29,35)(H,30,41)(H,36,37)(H,46,47)(H,48,49)(H2,28,31,32)(H2,43,44,45)/t14-,19-,20-,21+,25-,27+/m1/s1
InChI KeyCABVTRNMFUVUDM-VRHQGPGLSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as (s)-3-hydroxy-3-alkylglutaryl coas. These are 3-hydroxy-3-alkylglutaryl-CoAs where the 3-hydroxy-3-alkylglutaryl component has (S)-configuration.
KingdomOrganic compounds
Super ClassLipids and lipid-like molecules
ClassFatty Acyls
Sub ClassFatty acyl thioesters
Direct Parent(S)-3-hydroxy-3-alkylglutaryl CoAs
Alternative Parents
Substituents
  • Coenzyme a or derivatives
  • Purine ribonucleoside 3',5'-bisphosphate
  • Purine ribonucleoside bisphosphate
  • Purine ribonucleoside diphosphate
  • Ribonucleoside 3'-phosphate
  • Pentose phosphate
  • Pentose-5-phosphate
  • Beta amino acid or derivatives
  • Glycosyl compound
  • N-glycosyl compound
  • 6-aminopurine
  • Monosaccharide phosphate
  • Organic pyrophosphate
  • Pentose monosaccharide
  • Imidazopyrimidine
  • Purine
  • Monoalkyl phosphate
  • Aminopyrimidine
  • Alkyl phosphate
  • Imidolactam
  • N-acyl-amine
  • N-substituted imidazole
  • Organic phosphoric acid derivative
  • Monosaccharide
  • Fatty amide
  • Pyrimidine
  • Phosphoric acid ester
  • Tetrahydrofuran
  • Tertiary alcohol
  • Imidazole
  • Heteroaromatic compound
  • Azole
  • Secondary alcohol
  • Thiocarboxylic acid ester
  • Amino acid
  • Carboxamide group
  • Amino acid or derivatives
  • Carbothioic s-ester
  • Secondary carboxylic acid amide
  • Organoheterocyclic compound
  • Sulfenyl compound
  • Thiocarboxylic acid or derivatives
  • Azacycle
  • Oxacycle
  • Carboxylic acid derivative
  • Carboxylic acid
  • Monocarboxylic acid or derivatives
  • Organic oxygen compound
  • Primary amine
  • Hydrocarbon derivative
  • Carbonyl group
  • Organosulfur compound
  • Organopnictogen compound
  • Organic oxide
  • Organooxygen compound
  • Organonitrogen compound
  • Organic nitrogen compound
  • Alcohol
  • Amine
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Ontology
Disposition

Route of exposure:

Source:

Biological location:

Process

Naturally occurring process:

Role

Industrial application:

Biological role:

Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water SolubilityNot AvailableNot Available
LogPNot AvailableNot Available
Predicted Properties
PropertyValueSource
Water Solubility4.1 g/LALOGPS
logP-0.53ALOGPS
logP-6.4ChemAxon
logS-2.4ALOGPS
pKa (Strongest Acidic)0.82ChemAxon
pKa (Strongest Basic)3.81ChemAxon
Physiological Charge-5ChemAxon
Hydrogen Acceptor Count20ChemAxon
Hydrogen Donor Count11ChemAxon
Polar Surface Area421.16 ŲChemAxon
Rotatable Bond Count24ChemAxon
Refractivity193.7 m³·mol⁻¹ChemAxon
Polarizability82.37 ųChemAxon
Number of Rings3ChemAxon
BioavailabilityNoChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-000l-0891000250-052d51ef28faa9ab5b73Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-000i-0971100000-dc16942c0a4531c8cb60Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-000i-1950000000-12dcb50a3caaf20a9aa5Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-00o4-4901031462-49fbf273ff8df18347bbSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-001i-3900110010-0be1f0212b5d814ea24cSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-057i-6900100000-fffa063c59d4fcd54e7aSpectrum
Biological Properties
Cellular Locations
  • Cytoplasm
  • Extracellular
  • Membrane
  • Mitochondria
  • Endoplasmic reticulum
  • Peroxisome
Biospecimen LocationsNot Available
Tissue Locations
  • Adrenal Gland
  • Fibroblasts
  • Intestine
Pathways
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDNot Available
Phenol Explorer Compound IDNot Available
FooDB IDFDB030158
KNApSAcK IDC00007270
Chemspider ID392859
KEGG Compound IDC00356
BioCyc ID3-HYDROXY-3-METHYL-GLUTARYL-COA
BiGG IDNot Available
Wikipedia LinkNot Available
METLIN IDNot Available
PubChem Compound445127
PDB IDNot Available
ChEBI ID15467
Food Biomarker OntologyNot Available
VMH IDNot Available
MarkerDB ID
References
Synthesis ReferenceWilliamson I P; Rodwell V W Isolation and purification of 3-hydroxy-3-methylglutaryl-coenzyme A by ion-exchange chromatography. Journal of lipid research (1981), 22(1), 184-7.
Material Safety Data Sheet (MSDS)Not Available
General References
  1. Li X, Liu L, Tupper JC, Bannerman DD, Winn RK, Sebti SM, Hamilton AD, Harlan JM: Inhibition of protein geranylgeranylation and RhoA/RhoA kinase pathway induces apoptosis in human endothelial cells. J Biol Chem. 2002 May 3;277(18):15309-16. Epub 2002 Feb 11. [PubMed:11839765 ]
  2. Mital BK, Garg SK: Anticarcinogenic, hypocholesterolemic, and antagonistic activities of Lactobacillus acidophilus. Crit Rev Microbiol. 1995;21(3):175-214. [PubMed:8845062 ]
  3. Nozaki S, Nakagawa T, Nakata A, Yamashita S, Kameda-Takemura K, Nakamura T, Keno Y, Tokunaga K, Matsuzawa Y: Effects of pravastatin on plasma and urinary mevalonate concentrations in subjects with familial hypercholesterolaemia: a comparison of morning and evening administration. Eur J Clin Pharmacol. 1996;49(5):361-4. [PubMed:8866629 ]
  4. Ubels FL, Muntinga JH, van Doormaal JJ, Reitsma WD, Smit AJ: Effects of initial and long-term lipid-lowering therapy on vascular wall characteristics. Atherosclerosis. 2001 Jan;154(1):155-61. [PubMed:11137095 ]
  5. Huang L, Wang Y, Grimm S: ATP-dependent transport of rosuvastatin in membrane vesicles expressing breast cancer resistance protein. Drug Metab Dispos. 2006 May;34(5):738-42. Epub 2006 Jan 13. [PubMed:16415124 ]
  6. Sato T, Oouchi M, Nagakubo H, Chiba T, Ogawa S, Sato C, Sugimura K, Fukuda M: Effect of pravastatin on plasma ketone bodies in diabetics with hypercholesterolemia. Tohoku J Exp Med. 1998 May;185(1):25-9. [PubMed:9710942 ]
  7. Son BK, Kozaki K, Iijima K, Eto M, Kojima T, Ota H, Senda Y, Maemura K, Nakano T, Akishita M, Ouchi Y: Statins protect human aortic smooth muscle cells from inorganic phosphate-induced calcification by restoring Gas6-Axl survival pathway. Circ Res. 2006 Apr 28;98(8):1024-31. Epub 2006 Mar 23. [PubMed:16556867 ]
  8. Gianni L, Di Padova F, Zuin M, Podda M: Bile acid-induced inhibition of the lymphoproliferative response to phytohemagglutinin and pokeweed mitogen: an in vitro study. Gastroenterology. 1980 Feb;78(2):231-5. [PubMed:7350045 ]
  9. Jenke HS, Lowel M, Berndt J: Effect of alterations in vitro and in vivo of the cholesterol content in rat liver microsomes on the activity of 3-hydroxy-3-methylglutaryl-CoA reductase. Hoppe Seylers Z Physiol Chem. 1983 Feb;364(2):135-40. [PubMed:6840702 ]
  10. Naseem SM, Heald FP: Sex mediated lipid metabolism in human aortic smooth muscle cells. Biochem Biophys Res Commun. 1987 Apr 14;144(1):284-91. [PubMed:3579907 ]
  11. Wysocki SJ, Wilkinson SP, Hahnel R, Wong CY, Panegyres PK: 3-Hydroxy-3-methylglutaric aciduria, combined with 3-methylglutaconic aciduria. Clin Chim Acta. 1976 Aug 2;70(3):399-406. [PubMed:947633 ]
  12. Knight BL, Patel DD, Soutar AK: The regulation of 3-hydroxy-3-methylglutaryl-CoA reductase activity, cholesterol esterification and the expression of low-density lipoprotein receptors in cultured monocyte-derived macrophages. Biochem J. 1983 Feb 15;210(2):523-32. [PubMed:6305342 ]
  13. Lange Y, Ye J, Steck TL: Activation of membrane cholesterol by displacement from phospholipids. J Biol Chem. 2005 Oct 28;280(43):36126-31. Epub 2005 Aug 29. [PubMed:16129675 ]
  14. Martin J, Denver R, Bailey M, Krum H: In vitro inhibitory effects of atorvastatin on cardiac fibroblasts: implications for ventricular remodelling. Clin Exp Pharmacol Physiol. 2005 Sep;32(9):697-701. [PubMed:16173924 ]
  15. Plotkin D, Miller S, Nakajima S, Peskin E, Burkman R, Richardson D, Mitchel Y, Waldstreicher J, Liu M, Shapiro D, Santoro N: Lowering low density lipoprotein cholesterol with simvastatin, a hydroxy-3-methylglutaryl-coenzyme a reductase inhibitor, does not affect luteal function in premenopausal women. J Clin Endocrinol Metab. 2002 Jul;87(7):3155-61. [PubMed:12107216 ]
  16. Gil G, Smith JR, Goldstein JL, Brown MS: Optional exon in the 5'-untranslated region of 3-hydroxy-3-methylglutaryl coenzyme A synthase gene: conserved sequence and splicing pattern in humans and hamsters. Proc Natl Acad Sci U S A. 1987 Apr;84(7):1863-6. [PubMed:3470763 ]
  17. Freeman MR, Solomon KR: Cholesterol and prostate cancer. J Cell Biochem. 2004 Jan 1;91(1):54-69. [PubMed:14689582 ]

Enzymes

Enzyme Details
1. Hydroxymethylglutaryl-CoA lyase, mitochondrial
General function:
Involved in catalytic activity
Specific function:
Key enzyme in ketogenesis (ketone body formation). Terminal step in leucine catabolism.
Gene Name:
HMGCL
Uniprot ID:
P35914
Molecular weight:
34359.84
Reactions
3-Hydroxy-3-methylglutaryl-CoA → Acetyl-CoA + Acetoacetic aciddetails
Enzyme Details
2. Hydroxymethylglutaryl-CoA synthase, mitochondrial
General function:
Involved in hydroxymethylglutaryl-CoA synthase activity
Specific function:
This enzyme condenses acetyl-CoA with acetoacetyl-CoA to form HMG-CoA, which is the substrate for HMG-CoA reductase.
Gene Name:
HMGCS2
Uniprot ID:
P54868
Molecular weight:
52481.065
Reactions
Acetyl-CoA + Water + Acetoacetyl-CoA → 3-Hydroxy-3-methylglutaryl-CoA + Coenzyme Adetails
3-Hydroxy-3-methylglutaryl-CoA + Coenzyme A → Acetyl-CoA + Water + Acetoacetyl-CoAdetails
Enzyme Details
3. Hydroxymethylglutaryl-CoA synthase, cytoplasmic
General function:
Involved in hydroxymethylglutaryl-CoA synthase activity
Specific function:
This enzyme condenses acetyl-CoA with acetoacetyl-CoA to form HMG-CoA, which is the substrate for HMG-CoA reductase.
Gene Name:
HMGCS1
Uniprot ID:
Q01581
Molecular weight:
57293.105
Reactions
Acetyl-CoA + Water + Acetoacetyl-CoA → 3-Hydroxy-3-methylglutaryl-CoA + Coenzyme Adetails
3-Hydroxy-3-methylglutaryl-CoA + Coenzyme A → Acetyl-CoA + Water + Acetoacetyl-CoAdetails
Enzyme Details
4. 3-hydroxy-3-methylglutaryl-coenzyme A reductase
General function:
Involved in hydroxymethylglutaryl-CoA reductase (NADPH) activity
Specific function:
Transmembrane glycoprotein that is the rate-limiting enzyme in cholesterol biosynthesis as well as in the biosynthesis of nonsterol isoprenoids that are essential for normal cell function including ubiquinone and geranylgeranyl proteins.
Gene Name:
HMGCR
Uniprot ID:
P04035
Molecular weight:
97475.155
Reactions
Mevalonic acid + Coenzyme A + NADP → 3-Hydroxy-3-methylglutaryl-CoA + NADPHdetails
Mevalonic acid + Coenzyme A + NADP → 3-Hydroxy-3-methylglutaryl-CoA + NADPH + Hydrogen Iondetails
Enzyme Details
5. Methylglutaconyl-CoA hydratase, mitochondrial
General function:
Involved in catalytic activity
Specific function:
Catalyzes the conversion of 3-methylglutaconyl-CoA to 3-hydroxy-3-methylglutaryl-CoA. Has very low enoyl-CoA hydratase activity. Was originally identified as RNA-binding protein that binds in vitro to clustered 5'-AUUUA-3' motifs.
Gene Name:
AUH
Uniprot ID:
Q13825
Molecular weight:
35608.18
Reactions
3-Hydroxy-3-methylglutaryl-CoA → 3-Methylglutaconyl-CoA + Waterdetails
3-Hydroxy-3-methylglutaryl-CoA → 3-Methylglutaconyl-CoA + Waterdetails
Enzyme Details
6. 3-hydroxymethyl-3-methylglutaryl-CoA lyase, cytoplasmic
General function:
Involved in catalytic activity
Specific function:
Non-mitochondrial 3-hydroxymethyl-3-methylglutaryl-CoA lyase that catalyzes a cation-dependent cleavage of (S)-3-hydroxy-3-methylglutaryl-CoA into acetyl-CoA and acetoacetate, a key step in ketogenesis, the products of which support energy production in nonhepatic animal tissues.
Gene Name:
HMGCLL1
Uniprot ID:
Q8TB92
Molecular weight:
36327.465
Reactions
3-Hydroxy-3-methylglutaryl-CoA → Acetyl-CoA + Acetoacetic aciddetails