MiMeDB: Showing metabocard for Mevalonic acid (MMDBc0000506)

Microbial

Human

Plant

Pharmaceutical

Xenobiotic

Record Information

Version

2.0

Status

Detected and Quantified

Creation Date

2020-12-10 18:39:19 UTC

Update Date

2024-10-13 10:15:15 UTC

Metabolite ID

MMDBc0000506

Metabolite Identification

Common Name

Mevalonic acid

Description

Mevalonic acid, also known as MVA, mevalonate, or hiochic acid, belongs to the class of organic compounds known as hydroxy fatty acids. These are fatty acids in which the chain bears a hydroxyl group. Mevalonic acid is a key organic compound in biochemistry. It is found in most higher organisms ranging from plants to animals. Mevalonic acid is a precursor in the biosynthetic pathway known as the mevalonate pathway that produces terpenes (in plants) and steroids (in animals). Mevalonic acid is the primary precursor of isopentenyl pyrophosphate (IPP), that is in turn the basis for all terpenoids. The production of mevalonic acid by the enzyme 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, is the rate-limiting step in the biosynthesis of cholesterol (PMID: 12872277 ). The cholesterol biosynthetic pathway has three major steps: (1) acetate to mevalonate, (2) mevalonate to squalene, and (3) squalene to cholesterol. In the first step, which catalyzed by thiolase, two acetyl-CoA molecules form acetoacetyl-CoA and one CoA molecule is released, then the acetoacetyl-CoA reacts with another molecule of acetyl-CoA and generates 3-hydroxy-3-methylglutaryl-CoA (HMGCoA). The enzyme responsible for this reaction is 3-hydroxy-3-methylglutaryl-CoA synthase (HMG-CoA synthase): In the pathway to synthesize cholesterol, one of the HMG-CoA carboxyl groups undergoes reduction to an alcohol, releasing CoA, leading to the formation of mevalonate, a six carbon compound. This reaction is catalyzed by hydroxy-methylglutaryl-CoA reductase, In the second step (mevalonate to squalene) mevalonate receives a phosphoryl group from ATP to form 5-phosphomevalonate. This compound accepts another phosphate to generate mevalonate-5-pyrophosphate. After a third phosphorylation, the compound is decarboxylated, loses water, and generates isopentenyl pyrophosphate (IPP). Then through successive condensations, IPP forms squalene, a terpene hydrocarbon that contains 30 carbon atoms. By cyclization and other changes, this compound will finally result in cholesterol. Mevalonic acid is found, on average, in the highest concentration within a few different foods, such as apples, corns, and wild carrots and in a lower concentration in garden tomato (var.), pepper (C. frutescens), and cucumbers. Mevalonic acid has also been detected, but not quantified in, several different foods, such as sweet oranges, potato, milk (cow), cabbages, and white cabbages. This could make mevalonic acid a potential biomarker for the consumption of these foods. Plasma concentrations and urinary excretion of MVA are decreased by HMG-CoA reductase inhibitor drugs such as pravastatin, simvastatin, and atorvastatin (PMID: 8808497 ).

Structure

MOL SDF PDB SMILES InChI

Synonyms

Not Available

Molecular Formula

C₆H₁₂O₄

Average Mass

148.1571

Monoisotopic Mass

148.073558872

IUPAC Name

Not Available

Traditional Name

Not Available

CAS Registry Number

Not Available

SMILES

Not Available

InChI Identifier

InChI=1S/C6H12O4/c1-6(10,2-3-7)4-5(8)9/h7,10H,2-4H2,1H3,(H,8,9)/t6-/m1/s1

InChI Key

KJTLQQUUPVSXIM-ZCFIWIBFSA-N

Chemical Taxonomy

Functional Ontology

Not Available

Physical Properties

State

Expected Solid

Predicted Properties

Not Available

Spectra

Not Available

Chromatographic Retention Times and Retention Indices

Retention Times

Not Available

Retention Indices

Not Available

Biological Properties

Cellular Locations

Endoplasmic reticulum
Peroxisome

Biospecimen Locations

Blood
Feces
Fibroblasts
Leukocyte
Liver
Urine

Tissue Locations

Fibroblasts
Leukocyte
Liver

Associated OMIM IDs

114500 (Colorectal cancer)
610247 (Eosinophilic esophagitis)

Human Proteins and Enzymes

Protein ID	Protein Name	Protein Type	Uniprot ID	Species
MMDBp0192528	3-hydroxy-3-methylglutaryl-coenzyme A reductase	Enzyme	P04035	Homo sapiens
MMDBp0192662	Mevalonate kinase	Enzyme	Q03426	Homo sapiens

Human Pathways

Pathways

Name	SMPDB/PathBank

Microbial Pathways

Pathways

Not Available

Metabolic Reactions

Reactions

This table shows at most 20 reactions. For the full list of associated reactions:

See All Associated Reactions

Reaction ID	Precursor	Product	Enzyme	Reaction Type	Data Source	Reference
MMDBr0019903	Mevalonic acid	Mevalonic acid-5P	Mevalonate kinase	Phosphorylation	PathBank	31602464
MMDBr0019914	3-Hydroxy-3-methylglutaryl-CoA	Mevalonic acid	3-hydroxy-3-methylglutaryl-coenzyme A reductase 1	Reduction	PathBank	31602464
MMDBr0038939	Mevalonic acid	N-Mevalonyl-4R-hydroxysphinganine	Alkaline ceramidase YPC1	Hydrolysis	RHEA	34755880

Health Effects and Bioactivity

Health Outcome/Bioactivity	Metabolite Response/Effect	Evidence Type	Host and Biospecimen	Data Source	Reference
Mevalonic aciduria		Association	Human Blood	HMDB	8386351
Mevalonic aciduria		Association	Human Urine	HMDB	8386351
Smith-lemli-opitz syndrome	Decreased	Association	Human Blood	HMDB	10947201

Microbial Sources

Superkingdom/Kingdom	Phylum	Total species	Hosts and Body Sites	Microbial Links
Bacteria/Eubacteria	Verrucomicrobia	1	Human feces; Human stool; Human ; Human urine	Indirect association between microbiota composition and metabolites measured in host biospecimen
Bacteria/Eubacteria	Firmicutes	251	Human stool; Human ; Human feces; Human urine; Human sputum; Human saliva; Human supragingival plaque; Pig ; Cattle ; Human subgingival plaque	Indirect association between microbiota composition and metabolites measured in host biospecimen; Metabolic reconstruction
Archaea	Euryarchaeota	1	Human feces	Indirect association between microbiota composition and metabolites measured in host biospecimen
Archaea	Euryarchaeota	6	Human feces; Human	Indirect association between microbiota composition and metabolites measured in host biospecimen; Metabolic reconstruction
Bacteria/Eubacteria	Actinobacteria	71	Human ; Human feces; Human sputum; Human saliva; Human supragingival plaque; Human subgingival plaque; Human bronchial brush; Human nasopharyngeal swab; Human pleural fluid plaque; Human dental plaque; Human mucosa	Indirect association between microbiota composition and metabolites measured in host biospecimen; Metabolic reconstruction
Bacteria/Eubacteria	Proteobacteria	89	Human feces; Human sputum; Pig ; Human ; Human pleural fluid plaque; Human dental plaque; Human nasal swab	Metabolic reconstruction
Bacteria/Eubacteria	Bacteroidetes	64	Human feces; Human appendix biopsy; Human ; Human gastric fluid; Human saliva; Human subgingival plaque; Human supragingival plaque; Human stool	Metabolic reconstruction
Bacteria/Eubacteria	Spirochaetes	1	Human feces	Metabolic reconstruction
Archaea	Thaumarchaeota	1		Metabolic reconstruction
Bacteria	Firmicutes	1	Human stool; Human ; Human feces; Human urine; Human sputum; Human saliva; Human supragingival plaque; Pig ; Cattle ; Human subgingival plaque	Indirect association between microbiota composition and metabolites measured in host biospecimen; Metabolic reconstruction
Bacteria/Eubacteria	Fusobacteria	1	Human ; Human feces	Metabolic reconstruction
Bacteria/Eubacteria	Synergistetes	1	Human feces	Metabolic reconstruction
Bacteria/Eubacteria	Planctomycetes	1	Human feces	Metabolic reconstruction
Archaea	Crenarchaeota	1		Metabolic reconstruction
Eukaryota/Fungi	Ascomycota	1	Human feces; Human saliva	Unknown

Exposure Sources

Food Exposures

Other Exposures

Source Type	Data Source	Reference
Drugs - Antimicrobial	U.S. Environmental Protection Agency	CompTox
Cosmetics	U.S. Environmental Protection Agency	CompTox
Domestics	U.S. Environmental Protection Agency	CompTox

Host Biospecimen and Location

Host and Biospecimen	Status	Mean	Std	Min	Max	Units	Age	Sex	Health Condition	Data Source	Reference
Human Feces	Detected but not Quantified									HMDB
Human Blood	Detected and Quantified			20	140	uM	Children (1-13 years old)	Both	Mevalonic aciduria	HMDB	8386351
Human Urine	Detected and Quantified			2100	56000	umol/mmol creatinine	Infant (0-1 year old)	Both	Mevalonic aciduria	HMDB	8386351
Human Blood	Detected and Quantified			70	540	uM	Infant (0-1 year old)	Both	Mevalonic aciduria	HMDB	8386351
Human Urine	Detected and Quantified			900	14500	umol/mmol creatinine	Children (1-13 years old)	Both	Mevalonic aciduria	HMDB	8386351
Human Blood	Detected and Quantified	0.012	0.002			uM	Adult (>18 years old)	Both	Smith-Lemli-Opitz syndrome	HMDB	10947201
Human Urine	Detected and Quantified	0.0531				umol/mmol creatinine	Adult (>18 years old)	Both	Normal	HMDB	1653652
Human Urine	Detected and Quantified	0.0531				umol/mmol creatinine	Adult (>18 years old)	Both	Normal	HMDB	12872277
Human Urine	Detected and Quantified	0.5				umol/mmol creatinine	Adult (>18 years old)	Both	Normal	HMDB	12872277
Human Blood	Detected and Quantified	0.026		0.013	0.042	uM	Infant (0-1 year old)	Not Specified	Normal	HMDB	8386351
Human Blood	Detected and Quantified	0.028	0.006			uM	Adult (>18 years old)	Both	Normal	HMDB	10947201
Human Urine	Detected and Quantified	0.14		0.06	0.22	umol/mmol creatinine	Adult (>18 years old)	Both	Normal	HMDB	2702744
Human Urine	Detected and Quantified	0.160		0.0800	0.300	umol/mmol creatinine	Infant (0-1 year old)	Not Specified	Normal	HMDB	8386351
Human Urine	Detected and Quantified	0.178		0.0515	0.545	umol/mmol creatinine	Adult (>18 years old)	Both	Normal	HMDB	1653652
Human Urine	Detected and Quantified	0.178		0.0515	0.545	umol/mmol creatinine	Adult (>18 years old)	Both	Normal	HMDB	12872277
Human Blood	Detected and Quantified	0.043	0.013			uM	Adult (>18 years old)	Male	Normal	HMDB	Geigy Scientific Tables, 8th Rev edition, pp. 130. Edited by C. Lentner, West Cadwell, N.J.: Medical education Div., Ciba-Geigy Corp. Basel, Switzerland c1981-1992.
Human Fibroblasts	Detected but not Quantified						Not Specified	Not Specified	Normal	HMDB	34986597
Human Leukocyte	Detected but not Quantified						Not Specified	Not Specified	Normal	HMDB	34986597
Human Liver	Detected but not Quantified						Not Specified	Not Specified	Normal	HMDB	34986597
Human Feces	Detected but not Quantified						Adult (>18 years old)	Both	Normal	HMDB	27543620
Human Feces	Detected but not Quantified						Adult (>18 years old)	Both	Normal	HMDB	29808030
Human Urine	Detected but not Quantified						Adult (>18 years old)	Both	Normal	HMDB	32966057
Human Blood	Detected but not Quantified						Adult (>18 years old)	Both	Normal	HMDB	32966057

External Links

HMDB ID

Not Available

DrugBank ID

Not Available

Phenol Explorer Compound ID

Not Available

FooDB ID

Not Available

KNApSAcK ID

Not Available

Chemspider ID

Not Available

KEGG Compound ID

Not Available

BioCyc ID

Not Available

BiGG ID

Not Available

Wikipedia Link

Not Available

METLIN ID

Not Available

PubChem Compound

Not Available

PDB ID

Not Available

ChEBI ID

Not Available

Food Biomarker Ontology

Not Available

CMMC Knowledgebase

Not Available

General References

Hoffmann GF, Sweetman L, Bremer HJ, Hunneman DH, Hyanek J, Kozich V, Lehnert W, Nyhan WL, Speidel I, Trefz FK, et al.: Facts and artefacts in mevalonic aciduria: development of a stable isotope dilution GCMS assay for mevalonic acid and its application to physiological fluids, tissue samples, prenatal diagnosis and carrier detection. Clin Chim Acta. 1991 May 15;198(3):209-27. doi: 10.1016/0009-8981(91)90355-g. [PubMed:1653652 ]
Hoffmann G, Gibson KM, Brandt IK, Bader PI, Wappner RS, Sweetman L: Mevalonic aciduria--an inborn error of cholesterol and nonsterol isoprene biosynthesis. N Engl J Med. 1986 Jun 19;314(25):1610-4. doi: 10.1056/NEJM198606193142504. [PubMed:3012338 ]
Dmitrieva NA, Perrun'kina AM, Khomulo PS: [Determination of mevalonic acid in the urine and its concentration in the urine of patients with atherosclerosis]. Vopr Med Khim. 1968 Jan-Feb;14(1):106-8. [PubMed:5683362 ]
Larson RA, Kluskens LE, Yachnin S: The DNA synthetic response of normal and abnormal human lymphocytes to mevalonic acid: the role of granulocytes as a helper population. J Allergy Clin Immunol. 1984 Sep;74(3 Pt 1):280-90. doi: 10.1016/0091-6749(84)90259-8. [PubMed:6236250 ]
Mitchell ED Jr, Avigan J: Control of phosphorylation and decarboxylation of mevalonic acid and its metabolites in cultured human fibroblasts and in rat liver in vivo. J Biol Chem. 1981 Jun 25;256(12):6170-3. [PubMed:6263908 ]
Parker TS, McNamara DJ, Brown CD, Kolb R, Ahrens EH Jr, Alberts AW, Tobert J, Chen J, De Schepper PJ: Plasma mevalonate as a measure of cholesterol synthesis in man. J Clin Invest. 1984 Sep;74(3):795-804. doi: 10.1172/JCI111495. [PubMed:6565710 ]
Larson RA, Yachnin S: Mevalonic acid induces DNA synthesis in chronic lymphocytic leukemia cells. Blood. 1984 Jul;64(1):257-62. [PubMed:6610447 ]
Larson RA, Chung J, Scanu AM, Yachnin S: Neutrophils are required for the DNA synthetic response of human lymphocytes to mevalonic acid: evidence suggesting that a nonsterol product of mevalonate is involved. Proc Natl Acad Sci U S A. 1982 May;79(9):3028-32. doi: 10.1073/pnas.79.9.3028. [PubMed:6953445 ]
Siavoshian S, Simoneau C, Maugeais P, Marks L, Rodary L, Gardette J, Krempf M: Measurement of mevalonic acid in human urine by bench top gas chromatography-mass spectrometry. Clin Chim Acta. 1995 Dec 29;243(2):129-36. doi: 10.1016/0009-8981(95)06162-2. [PubMed:8747489 ]
Naoumova RP, Marais AD, Mountney J, Firth JC, Rendell NB, Taylor GW, Thompson GR: Plasma mevalonic acid, an index of cholesterol synthesis in vivo, and responsiveness to HMG-CoA reductase inhibitors in familial hypercholesterolaemia. Atherosclerosis. 1996 Jan 26;119(2):203-13. doi: 10.1016/0021-9150(95)05649-1. [PubMed:8808497 ]
Houten SM, Kuis W, Duran M, de Koning TJ, van Royen-Kerkhof A, Romeijn GJ, Frenkel J, Dorland L, de Barse MM, Huijbers WA, Rijkers GT, Waterham HR, Wanders RJ, Poll-The BT: Mutations in MVK, encoding mevalonate kinase, cause hyperimmunoglobulinaemia D and periodic fever syndrome. Nat Genet. 1999 Jun;22(2):175-7. doi: 10.1038/9691. [PubMed:10369261 ]
Lindenthal B, von Bergmann K: Urinary excretion and serum concentration of mevalonic acid during acute intake of alcohol. Metabolism. 2000 Jan;49(1):62-6. doi: 10.1016/s0026-0495(00)90713-3. [PubMed:10647065 ]
Simons K, Toomre D: Lipid rafts and signal transduction. Nat Rev Mol Cell Biol. 2000 Oct;1(1):31-9. doi: 10.1038/35036052. [PubMed:11413487 ]
Haas D, Kelley RI, Hoffmann GF: Inherited disorders of cholesterol biosynthesis. Neuropediatrics. 2001 Jun;32(3):113-22. doi: 10.1055/s-2001-16618. [PubMed:11521206 ]
Abrar M, Martin PD: Validation and application of an assay for the determination of mevalonic acid in human plasma by liquid chromatography tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2002 Jun 25;773(2):103-11. doi: 10.1016/s1570-0232(02)00131-9. [PubMed:12031835 ]
Jemal M, Schuster A, Whigan DB: Liquid chromatography/tandem mass spectrometry methods for quantitation of mevalonic acid in human plasma and urine: method validation, demonstration of using a surrogate analyte, and demonstration of unacceptable matrix effect in spite of use of a stable isotope analog internal standard. Rapid Commun Mass Spectrom. 2003;17(15):1723-34. doi: 10.1002/rcm.1112. [PubMed:12872277 ]
Watson AD: Thematic review series: systems biology approaches to metabolic and cardiovascular disorders. Lipidomics: a global approach to lipid analysis in biological systems. J Lipid Res. 2006 Oct;47(10):2101-11. doi: 10.1194/jlr.R600022-JLR200. Epub 2006 Aug 10. [PubMed:16902246 ]
Sethi JK, Vidal-Puig AJ: Thematic review series: adipocyte biology. Adipose tissue function and plasticity orchestrate nutritional adaptation. J Lipid Res. 2007 Jun;48(6):1253-62. doi: 10.1194/jlr.R700005-JLR200. Epub 2007 Mar 20. [PubMed:17374880 ]
Lingwood D, Simons K: Lipid rafts as a membrane-organizing principle. Science. 2010 Jan 1;327(5961):46-50. doi: 10.1126/science.1174621. [PubMed:20044567 ]
Gunstone, Frank D., John L. Harwood, and Albert J. Dijkstra (2007). The lipid handbook with CD-ROM. CRC Press.

Showing metabocard for Mevalonic acid (MMDBc0000506)

MOL for #<Metabolite:0x000056153740e910>

3D MOL for #<Metabolite:0x000056153740e910>

3D SDF for #<Metabolite:0x000056153740e910>

3D-SDF for #<Metabolite:0x000056153740e910>

PDB for #<Metabolite:0x000056153740e910>

3D PDB for #<Metabolite:0x000056153740e910>

SMILES for #<Metabolite:0x000056153740e910>

INCHI for #<Metabolite:0x000056153740e910>

Structure for #<Metabolite:0x000056153740e910>

3D Structure for #<Metabolite:0x000056153740e910>