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MetaCyc Pathway: mevalonate pathway I
Inferred from experimentTraceable author statement to experimental support

Enzyme View:

Pathway diagram: mevalonate pathway I

This view shows enzymes only for those organisms listed below, in the list of taxa known to possess the pathway. If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.

Synonyms: isoprenoid pathway, MVA pathway, isopentenyl diphosphate biosynthesis, dimethylallyl diphosphate biosynthesis

Superclasses: BiosynthesisSecondary Metabolites BiosynthesisTerpenoids BiosynthesisHemiterpenes BiosynthesisIsopentenyl Diphosphate Biosynthesis

Some taxa known to possess this pathway include : Arabidopsis thaliana col, Catharanthus roseus, Homo sapiens, Nicotiana tabacum, Saccharomyces cerevisiae

Expected Taxonomic Range: Archaea, Bacteria , Fungi, Metazoa, Viridiplantae

General Background

The biosynthesis of isopentenyl diphosphate (IPP) can occur via two distinct routes: the mevalonate pathway I (MVA pathway, this pathway) and the methylerythritol phosphate pathway I (MEP pathway). In the former, IPP is synthesized from the condensation of three acetyl-CoA molecules; in contrast, in the MEP pathway IPP is synthesized via the condensation of pyruvate and D-glyceraldehyde 3-phosphate.

For many years, the MVA pathway was considered to be the sole source of IPP in all living organisms, however, several inconsistencies led to the discovery of the MEP pathway in bacteria and plants. The MEP pathway is present in most eubacteria, in unicellular green algae, in the chloroplasts of phototrophic organisms and in some unicellular eukaryotes related to photosynthetic phyla, such as the Plasmodium parasites.

The mevalonate pathway is found in animals, fungi, the cytoplasm of phototrophic organisms, archaea, and some eubacteria.

About This Pathway

In eukaryotic cells, the mevalonate pathway leads to plant sterol biosynthesis, ergosterol biosynthesis I and dolichol biosynthesis via the formation of farnesyl diphosphate (FPP). IPP from this pathway is also used to synthesize cytosolic geranylgeranyl diphosphate (GGPP) which is used (along with FPP) for the prenylation of proteins. In plants, the mevalonate pathway is also a source of isoprene units for the biosynthesis of a variety of terpenoids (cytokinins, brassinosteroids, sesquiterpenes, polyprenoids).

All the enzymes of this pathway have been isolated from bacteria. Additionally, a number of plant homologues have been demonstrated to be fully functional, largely through functional complementation of bacterial and yeast mutant strains.

Citations: [Daum98, Zhong05, Kuzuyama02]

Superpathways: superpathway of geranylgeranyldiphosphate biosynthesis I (via mevalonate), superpathway of cholesterol biosynthesis, superpathway of ergosterol biosynthesis I, Methanobacterium thermoautotrophicum biosynthetic metabolism

Variants: methylerythritol phosphate pathway I, methylerythritol phosphate pathway II, mevalonate pathway II (archaea), mevalonate pathway III (archaea)

Unification Links: AraCyc:PWY-922

Created 13-Aug-2001 by Pellegrini-Toole A, Marine Biological Laboratory


Daum98: Daum G, Lees ND, Bard M, Dickson R (1998). "Biochemistry, cell biology and molecular biology of lipids of Saccharomyces cerevisiae." Yeast 1998;14(16);1471-510. PMID: 9885152

Kuzuyama02: Kuzuyama T (2002). "Mevalonate and nonmevalonate pathways for the biosynthesis of isoprene units." Biosci Biotechnol Biochem 66(8);1619-27. PMID: 12353619

Zhong05: Zhong JJ, Yue CJ (2005). "Plant cells: secondary metabolite heterogeneity and its manipulation." Adv Biochem Eng Biotechnol 100;53-88. PMID: 16270656

Other References Related to Enzymes, Genes, Subpathways, and Substrates of this Pathway

Alber06: Alber BE, Spanheimer R, Ebenau-Jehle C, Fuchs G (2006). "Study of an alternate glyoxylate cycle for acetate assimilation by Rhodobacter sphaeroides." Mol Microbiol 61(2);297-309. PMID: 16856937

Aledo01: Aledo R, Zschocke J, Pie J, Mir C, Fiesel S, Mayatepek E, Hoffmann GF, Casals N, Hegardt FG (2001). "Genetic basis of mitochondrial HMG-CoA synthase deficiency." Hum Genet 109(1);19-23. PMID: 11479731

Anderson89: Anderson MS, Muehlbacher M, Street IP, Proffitt J, Poulter CD (1989). "Isopentenyl diphosphate:dimethylallyl diphosphate isomerase. An improved purification of the enzyme and isolation of the gene from Saccharomyces cerevisiae." J Biol Chem 1989;264(32);19169-75. PMID: 2681212

Bairoch93a: Bairoch A, Boeckmann B (1993). "The SWISS-PROT protein sequence data bank, recent developments." Nucleic Acids Res. 21:3093-3096. PMID: 8332529

Bard81: Bard M, Downing JF (1981). "Genetic and biochemical aspects of yeast sterol regulation involving 3-hydroxy-3-methylglutaryl coenzyme A reductase." J Gen Microbiol 1981;125(Pt 2);415-20. PMID: 7033470

Barker82: Barker HA, Kahn JM, Hedrick L (1982). "Pathway of lysine degradation in Fusobacterium nucleatum." J Bacteriol 152(1);201-7. PMID: 6811551

Basson86: Basson ME, Thorsness M, Rine J (1986). "Saccharomyces cerevisiae contains two functional genes encoding 3-hydroxy-3-methylglutaryl-coenzyme A reductase." Proc Natl Acad Sci U S A 1986;83(15);5563-7. PMID: 3526336

Bennett84: Bennett MJ, Hosking GP, Smith MF, Gray RG, Middleton B (1984). "Biochemical investigations on a patient with a defect in cytosolic acetoacetyl-CoA thiolase, associated with mental retardation." J Inherit Metab Dis 7(3);125-8. PMID: 6150136

Berg07: Berg IA, Kockelkorn D, Buckel W, Fuchs G (2007). "A 3-hydroxypropionate/4-hydroxybutyrate autotrophic carbon dioxide assimilation pathway in Archaea." Science 318(5857);1782-6. PMID: 18079405

Berges97: Berges T, Guyonnet D, Karst F (1997). "The Saccharomyces cerevisiae mevalonate diphosphate decarboxylase is essential for viability, and a single Leu-to-Pro mutation in a conserved sequence leads to thermosensitivity." J Bacteriol 1997;179(15);4664-70. PMID: 9244250

Bochar97: Bochar DA, Brown JR, Doolittle WF, Klenk HP, Lam W, Schenk ME, Stauffacher CV, Rodwell VW (1997). "3-hydroxy-3-methylglutaryl coenzyme A reductase of Sulfolobus solfataricus: DNA sequence, phylogeny, expression in Escherichia coli of the hmgA gene, and purification and kinetic characterization of the gene product." J Bacteriol 179(11);3632-8. PMID: 9171410

Bonanno01: Bonanno JB, Edo C, Eswar N, Pieper U, Romanowski MJ, Ilyin V, Gerchman SE, Kycia H, Studier FW, Sali A, Burley SK (2001). "Structural genomics of enzymes involved in sterol/isoprenoid biosynthesis." Proc Natl Acad Sci U S A 98(23);12896-901. PMID: 11698677

Bouchard01: Bouchard L, Robert MF, Vinarov D, Stanley CA, Thompson GN, Morris A, Leonard JV, Quant P, Hsu BY, Boneh A, Boukaftane Y, Ashmarina L, Wang S, Miziorko H, Mitchell GA (2001). "Mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase deficiency: clinical course and description of causal mutations in two patients." Pediatr Res 49(3);326-31. PMID: 11228257

Boukaftane94: Boukaftane Y, Duncan A, Wang S, Labuda D, Robert MF, Sarrazin J, Schappert K, Mitchell GA (1994). "Human mitochondrial HMG CoA synthase: liver cDNA and partial genomic cloning, chromosome mapping to 1p12-p13, and possible role in vertebrate evolution." Genomics 23(3);552-9. PMID: 7851882

Boukaftane97: Boukaftane Y, Mitchell GA (1997). "Cloning and characterization of the human mitochondrial 3-hydroxy-3-methylglutaryl CoA synthase gene." Gene 195(2);121-6. PMID: 9305755

Breitling03: Breitling R, Laubner D, Clizbe D, Adamski J, Krisans SK (2003). "Isopentenyl-diphosphate isomerases in human and mouse: evolutionary analysis of a mammalian gene duplication." J Mol Evol 57(3);282-91. PMID: 14629038

BRENDA14: BRENDA team (2014). Imported from BRENDA version existing on Aug 2014.

Campbell98: Campbell M, Hahn FM, Poulter CD, Leustek T (1998). "Analysis of the isopentenyl diphosphate isomerase gene family from Arabidopsis thaliana." Plant Mol Biol 36(2);323-8. PMID: 9484444

Carrigan03: Carrigan CN, Poulter CD (2003). "Zinc is an essential cofactor for type I isopentenyl diphosphate:dimethylallyl diphosphate isomerase." J Am Chem Soc 125(30);9008-9. PMID: 15369345

Chambliss96: Chambliss KL, Slaughter CA, Schreiner R, Hoffmann GF, Gibson KM (1996). "Molecular cloning of human phosphomevalonate kinase and identification of a consensus peroxisomal targeting sequence." J Biol Chem 271(29);17330-4. PMID: 8663599

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Report Errors or Provide Feedback
Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
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