MetaCyc Pathway: superpathway of geranylgeranyldiphosphate biosynthesis I (via mevalonate)

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: GGPP biosynthesis

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

Expected Taxonomic Range: Bacteria , Eukaryota

Summary:
all-trans-geranylgeranyl diphosphate (also known as geranylgeranyl pyrophosphate, or GGPP) is a crucial compound involved in the biosynthesis of a variety of terpenes and terpenoids, including central compounds such as ubiquinones and menaquinones.

In plants, all-trans-geranylgeranyl diphosphate is an intermediate in the biosynthesis of essentail compounds such as chlorophylls, carotenoids, tocopherols, plastoquinones, and gibberellins [RodriguezC02], as well as a variety of secondary metabolites.

In addition, GGPP is also used in posttranslational modifications of proteins (geranylgeranylation) which is important for membrane adhesion as well as the function of some proteins [Caldelari01, Johnson05a].

GGPP is synthesized from (2E,6E)-farnesyl diphosphate either by dedicated enzymes, such as the farnesyltranstransferase of Saccharomyces cerevisiae S288c, or by the action of polyprenyl transferases such as the solanesyl diphosphate synthase from Rhodobacter capsulatus or octaprenyl diphosphate synthase from Escherichia coli K-12. It should be noted that the building blocks for (2E,6E)-farnesyl diphosphate are synthesized in different organisms by different pathways. While most eukaryotes and some bacteria use the mevalonate pathway I, most bacteria, as well as green algae utilize the methylerythritol phosphate pathway (as described in the two superpathways superpathway of geranylgeranyldiphosphate biosynthesis I (via mevalonate) and superpathway of geranylgeranyldiphosphate biosynthesis II (via MEP)).

In plants, GGPP is synthesized using both routes - in the cytosol using the mevalonate pathway I, and in the plastids using the methylerythritol phosphate pathway.

This superpathway describes the production of GGPP via the mevalonate pathway I. In plants, cytosolic GGPP is mainly used in the geranylgeranylation of proteins.

Superpathways: Methanobacterium thermoautotrophicum biosynthetic metabolism

Subpathways: mevalonate pathway I , trans, trans-farnesyl diphosphate biosynthesis , geranylgeranyldiphosphate biosynthesis

Credits:
Created 01-May-2008 by Caspi R , SRI International

References

Caldelari01: Caldelari D, Sternberg H, Rodriguez-Concepcion M, Gruissem W, Yalovsky S (2001). "Efficient prenylation by a plant geranylgeranyltransferase-I requires a functional CaaL box motif and a proximal polybasic domain." Plant Physiol 126(4);1416-29. PMID: 11500541

Johnson05a: Johnson CD, Chary SN, Chernoff EA, Zeng Q, Running MP, Crowell DN (2005). "Protein geranylgeranyltransferase I is involved in specific aspects of abscisic acid and auxin signaling in Arabidopsis." Plant Physiol 139(2);722-33. PMID: 16183844

Okada00a: Okada K, Saito T, Nakagawa T, Kawamukai M, Kamiya Y (2000). "Five geranylgeranyl diphosphate synthases expressed in different organs are localized into three subcellular compartments in Arabidopsis." Plant Physiol 122(4);1045-56. PMID: 10759500

RodriguezC02: Rodriguez-Concepcion M, Boronat A (2002). "Elucidation of the methylerythritol phosphate pathway for isoprenoid biosynthesis in bacteria and plastids. A metabolic milestone achieved through genomics." Plant Physiol 130(3);1079-89. PMID: 12427975

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

Aharoni03: Aharoni A, Giri AP, Deuerlein S, Griepink F, de Kogel WJ, Verstappen FW, Verhoeven HA, Jongsma MA, Schwab W, Bouwmeester HJ (2003). "Terpenoid metabolism in wild-type and transgenic Arabidopsis plants." Plant Cell 15(12);2866-84. PMID: 14630967

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

Anderson89a: 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

Anderson89b: Anderson MS, Yarger JG, Burck CL, Poulter CD (1989). "Farnesyl diphosphate synthetase. Molecular cloning, sequence, and expression of an essential gene from Saccharomyces cerevisiae." J Biol Chem 1989;264(32);19176-84. PMID: 2681213

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

Barnard81: Barnard GF, Popjak G (1981). "Human liver prenyltransferase and its characterization." Biochim Biophys Acta 661(1);87-99. PMID: 7295734

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

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

Bouvier00: Bouvier F, Suire C, d'Harlingue A, Backhaus RA, Camara B (2000). "Molecular cloning of geranyl diphosphate synthase and compartmentation of monoterpene synthesis in plant cells." Plant J 24(2);241-52. PMID: 11069698

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

Burke02: Burke C, Croteau R (2002). "Interaction with the small subunit of geranyl diphosphate synthase modifies the chain length specificity of geranylgeranyl diphosphate synthase to produce geranyl diphosphate." J Biol Chem 277(5);3141-9. PMID: 11733504

Burke04: Burke C, Klettke K, Croteau R (2004). "Heteromeric geranyl diphosphate synthase from mint: construction of a functional fusion protein and inhibition by bisphosphonate substrate analogs." Arch Biochem Biophys 422(1);52-60. PMID: 14725857

Burke99: Burke CC, Wildung MR, Croteau R (1999). "Geranyl diphosphate synthase: cloning, expression, and characterization of this prenyltransferase as a heterodimer." Proc Natl Acad Sci U S A 96(23);13062-7. PMID: 10557273

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