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Record Information
Version4.0
Creation Date2005-11-16 15:48:42 UTC
Update Date2017-09-27 08:13:15 UTC
HMDB IDHMDB0001375
Secondary Accession Numbers
  • HMDB01375
Metabolite Identification
Common Name3-Hydroxy-3-methylglutaryl-CoA
Description3-hydroxy-3-methylglutaryl CoA (HMG-CoA) 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
Thumb
Synonyms
ValueSource
(S)-3-Hydroxy-3-methylglutaryl-CoAHMDB
(S)-3-Hydroxy-3-methylglutaryl-coenzyme AHMDB
3-Hydroxy-3-methyl-glutaryl-CoAHMDB
3-Hydroxy-3-methyl-glutaryl-coenzyme AHMDB
3-Hydroxy-3-methylglutaryl-coenzyme AHMDB
HMG-CoAHMDB
HMG-coenzyme AHMDB
Hydroxymethylglutaroyl coenzyme AHMDB
Hydroxymethylglutaryl-CoAHMDB
Hydroxymethylglutaryl-coenzyme AHMDB
S-(Hydrogen 3-hydroxy-3-methylglutaryl)coenzyme AHMDB
S-(Hydrogen 3-hydroxy-3-methylpentanedioateHMDB
S-(Hydrogen 3-hydroxy-3-methylpentanedioate) coenzyme AHMDB
S-(Hydrogen 3-hydroxy-3-methylpentanedioic acidHMDB
3-Hydroxy-3-methylglutaryl-coenzyme A, (S)-isomerMeSH
3-Hydroxy-3-methylglutaryl-coenzyme A, mono(3-oxobutanoate)MeSH
Chemical FormulaC27H44N7O20P3S
Average Molecular Weight911.659
Monoisotopic Molecular Weight911.157467109
IUPAC Name(3S)-5-{[2-(3-{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 Name(3S)-5-({2-[3-(3-{[({[(2R,3S,4R,5R)-5-(6-aminopurin-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
CAS Registry Number1553-55-5
SMILES
C[C@](O)(CC(O)=O)CC(=O)SCCNC(=O)CCNC(=O)C(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-MIGRVSMKSA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of chemical entities known as 3-hydroxy-3-alkylglutaryl coas. These are alpha, omega dicarboxyacyl-CoA that result from the formal condensation of the thiol group of coenzyme A with one of the carboxy groups of 3-hydroxy-3-alkylglutaric acid.
KingdomChemical entities
Super ClassOrganic compounds
ClassLipids and lipid-like molecules
Sub ClassFatty Acyls
Direct Parent3-hydroxy-3-alkylglutaryl CoAs
Alternative Parents
Substituents
  • Coenzyme a or derivatives
  • Purine ribonucleoside 3',5'-bisphosphate
  • Purine ribonucleoside bisphosphate
  • Purine ribonucleoside diphosphate
  • Pentose phosphate
  • Pentose-5-phosphate
  • Ribonucleoside 3'-phosphate
  • Beta amino acid or derivatives
  • Glycosyl compound
  • N-glycosyl compound
  • Monosaccharide phosphate
  • Organic pyrophosphate
  • 6-aminopurine
  • Pentose monosaccharide
  • Imidazopyrimidine
  • Purine
  • Monoalkyl phosphate
  • Aminopyrimidine
  • Fatty amide
  • Imidolactam
  • Monosaccharide
  • N-acyl-amine
  • N-substituted imidazole
  • Organic phosphoric acid derivative
  • Alkyl phosphate
  • Phosphoric acid ester
  • Primary aromatic amine
  • Pyrimidine
  • Tertiary alcohol
  • Heteroaromatic compound
  • Imidazole
  • Azole
  • Oxolane
  • Carboxamide group
  • Carbothioic s-ester
  • Secondary alcohol
  • Amino acid
  • Secondary carboxylic acid amide
  • Amino acid or derivatives
  • Thiocarboxylic acid ester
  • Organoheterocyclic compound
  • Carboxylic acid
  • Monocarboxylic acid or derivatives
  • Azacycle
  • Oxacycle
  • Thiocarboxylic acid or derivatives
  • Sulfenyl compound
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organic nitrogen compound
  • Alcohol
  • Amine
  • Organonitrogen compound
  • Carbonyl group
  • Organooxygen compound
  • Organosulfur compound
  • Organic oxygen compound
  • Organopnictogen compound
  • Primary amine
  • Organic oxide
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot Available
Ontology
Disposition

Biological Location:

  Subcellular:

  Biofluid and excreta:

  Organ and components:

    Endocrine gland:

  Cell and elements:

    Cell:

Source:

  Biological:

    Animal:

Route of exposure:

  Enteral:

Process

Naturally occurring process:

  Biological process:

    Biochemical pathway:

    Cellular process:

    Chemical reaction:

    Biochemical process:

Role

Indirect biological 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-7.5ChemAxon
logS-2.4ALOGPS
pKa (Strongest Acidic)0.83ChemAxon
pKa (Strongest Basic)5ChemAxon
Physiological Charge-5ChemAxon
Hydrogen Acceptor Count20ChemAxon
Hydrogen Donor Count11ChemAxon
Polar Surface Area421.16 ŲChemAxon
Rotatable Bond Count24ChemAxon
Refractivity193.7 m³·mol⁻¹ChemAxon
Polarizability81.01 ųChemAxon
Number of Rings3ChemAxon
Bioavailability0ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-000l-0891000250-052d51ef28faa9ab5b73View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-000i-0971100000-dc16942c0a4531c8cb60View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-000i-1950000000-12dcb50a3caaf20a9aa5View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-00o4-4901031462-49fbf273ff8df18347bbView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-001i-3900110010-0be1f0212b5d814ea24cView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-057i-6900100000-fffa063c59d4fcd54e7aView in MoNA
Biological Properties
Cellular Locations
  • Cytoplasm
  • Extracellular
  • Membrane
  • Mitochondria
  • Endoplasmic reticulum
  • Peroxisome
Biofluid LocationsNot Available
Tissue Location
  • Adrenal Gland
  • Fibroblasts
  • Intestine
Pathways
NameSMPDB/PathwhizKEGG
2-Methyl-3-Hydroxybutryl CoA Dehydrogenase DeficiencyPw000061Pw000061 greyscalePw000061 simpleNot Available
3-Hydroxy-3-Methylglutaryl-CoA Lyase DeficiencyPw000063Pw000063 greyscalePw000063 simpleNot Available
3-Methylcrotonyl Coa Carboxylase Deficiency Type IPw000065Pw000065 greyscalePw000065 simpleNot Available
3-Methylglutaconic Aciduria Type IPw000066Pw000066 greyscalePw000066 simpleNot Available
3-Methylglutaconic Aciduria Type IIIPw000067Pw000067 greyscalePw000067 simpleNot Available
Displaying entries 1 - 5 of 43 in total
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDNot Available
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDFDB022587
KNApSAcK IDNot Available
Chemspider ID388357
KEGG Compound IDC00356
BioCyc ID3-HYDROXY-3-METHYL-GLUTARYL-COA
BiGG ID34727
Wikipedia Link3-hydroxy-3-methylglutaryl-CoA
METLIN ID6201
PubChem Compound439218
PDB ID1DQ9
ChEBI ID15467
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. 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 ]
  2. 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 ]
  3. 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 ]
  4. 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 ]
  5. Mital BK, Garg SK: Anticarcinogenic, hypocholesterolemic, and antagonistic activities of Lactobacillus acidophilus. Crit Rev Microbiol. 1995;21(3):175-214. [PubMed:8845062 ]
  6. 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 ]
  7. 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 ]
  8. 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 ]
  9. 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 ]
  10. 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 ]
  11. 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 ]
  12. 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 ]
  13. 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 ]
  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

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
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
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
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
(R)-mevalonate + Coenzyme A + NADP → 3-Hydroxy-3-methylglutaryl-CoA + NADPHdetails
(R)-mevalonate + Coenzyme A + NADP → 3-Hydroxy-3-methylglutaryl-CoA + NADPH + Hydrogen Iondetails
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
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