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:||Biosynthesis → Secondary Metabolites Biosynthesis → Terpenoids Biosynthesis → Hemiterpenes Biosynthesis → Isopentenyl Diphosphate Biosynthesis|
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.
Superpathways: superpathway of geranylgeranyldiphosphate biosynthesis I (via mevalonate), superpathway of cholesterol biosynthesis, superpathway of ergosterol biosynthesis I, Methanobacterium thermoautotrophicum biosynthetic metabolism
Unification Links: AraCyc:PWY-922
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
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
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
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
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
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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