ENTRY       hsa00900                    Pathway
NAME        Terpenoid backbone biosynthesis - Homo sapiens (human)
DESCRIPTION Terpenoids, also known as isoprenoids, are a large class of natural products consisting of isoprene (C5) units. There are two biosynthetic pathways, the mevalonate pathway [MD:M00095] and the non-mevalonate pathway or the MEP/DOXP pathway [MD:M00096], for the terpenoid building blocks: isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP). The action of prenyltransferases then generates higher-order building blocks: geranyl diphosphate (GPP), farsenyl diphosphate (FPP), and geranylgeranyl diphosphate (GGPP), which are the precursors of monoterpenoids (C10), sesquiterpenoids (C15), and diterpenoids (C20), respectively. Condensation of these building blocks gives rise to the precursors of sterols (C30) and carotenoids (C40). The MEP/DOXP pathway is absent in higher animals and fungi, but in green plants the MEP/DOXP and mevalonate pathways co-exist in separate cellular compartments. The MEP/DOXP pathway, operating in the plastids, is responsible for the formation of essential oil monoterpenes and linalyl acetate, some sesquiterpenes, diterpenes, and carotenoids and phytol. The mevalonate pathway, operating in the cytosol, gives rise to triterpenes, sterols, and most sesquiterpenes.
CLASS       Metabolism; Metabolism of terpenoids and polyketides
PATHWAY_MAP hsa00900  Terpenoid backbone biosynthesis
MODULE      hsa_M00095  C5 isoprenoid biosynthesis, mevalonate pathway [PATH:hsa00900]
            hsa_M00367  C10-C20 isoprenoid biosynthesis, non-plant eukaryotes [PATH:hsa00900]
NETWORK     nt06015  N-Glycan biosynthesis
  ELEMENT   N00675  N-Glycan precursor biosynthesis, farnesy-PP to P-Dol
DRUG        D00359  Lovastatin (USP/INN)
            D00434  Simvastatin (JP18/USP/INN)
            D00887  Atorvastatin calcium anhydorous
            D00889  Cerivastatin sodium (JAN/USAN)
            D00892  Fluvastatin sodium (JAN/USP)
            D00893  Pravastatin sodium (JP18/USP)
            D00939  Alendronate sodium (USP)
            D00941  Pamidronate disodium (USP)
            D00942  Risedronate sodium (USP)
            D01862  Pitavastatin calcium (JAN)
            D01915  Rosuvastatin calcium (JP18/USP)
            D01968  Zoledronic acid (USAN)
            D02258  Atorvastatin calcium (USP)
            D03234  Sodium risedronate hydrate (JP18)
            D03601  Crilvastatin (USAN/INN)
            D03643  Dalvastatin (USAN/INN)
            D03720  Tipifarnib (USAN/INN)
            D03816  Tenivastatin calcium (USAN)
            D04486  Ibandronate sodium (USAN)
            D04768  Lonafarnib (USAN/INN)
            D06378  Zoledronate disodium (USAN)
            D06379  Zoledronate trisodium (USAN)
            D07119  Alendronic acid (INN)
            D07123  Incadronate disodium hydrate (JAN)
            D07281  Pamidronic acid (INN)
            D07474  Atorvastatin (INN)
            D07661  Cerivastatin (INN)
            D07983  Fluvastatin (INN)
            D08056  Ibandronic acid (INN)
            D08073  Incadronic acid (INN)
            D08410  Pravastatin (INN)
            D08484  Risedronic acid (INN)
            D08492  Rosuvastatin (INN)
            D08689  Zoledronic acid (INN)
            D09198  Minodronic acid hydrate (JAN)
            D10515  Zoledronic acid hemipentahydrate (JAN)
            D10568  Pitavastatin calcium hydrate (JP18)
            D11092  Pitavastatin magnesium
            D11095  Atorvastatin calcium propylene glycol solvate
            D11570  Risedronate sodium monohydrate
DBLINKS     GO: 0009240 0016091
ORGANISM    Homo sapiens (human) [GN:hsa]
GENE        39  ACAT2; acetyl-CoA acetyltransferase 2 [KO:K00626] [EC:2.3.1.9]
            38  ACAT1; acetyl-CoA acetyltransferase 1 [KO:K00626] [EC:2.3.1.9]
            3157  HMGCS1; 3-hydroxy-3-methylglutaryl-CoA synthase 1 [KO:K01641] [EC:2.3.3.10]
            3158  HMGCS2; 3-hydroxy-3-methylglutaryl-CoA synthase 2 [KO:K01641] [EC:2.3.3.10]
            3156  HMGCR; 3-hydroxy-3-methylglutaryl-CoA reductase [KO:K00021] [EC:1.1.1.34]
            4598  MVK; mevalonate kinase [KO:K00869] [EC:2.7.1.36]
            10654  PMVK; phosphomevalonate kinase [KO:K13273] [EC:2.7.4.2]
            4597  MVD; mevalonate diphosphate decarboxylase [KO:K01597] [EC:4.1.1.33]
            3422  IDI1; isopentenyl-diphosphate delta isomerase 1 [KO:K01823] [EC:5.3.3.2]
            91734  IDI2; isopentenyl-diphosphate delta isomerase 2 [KO:K01823] [EC:5.3.3.2]
            2224  FDPS; farnesyl diphosphate synthase [KO:K00787] [EC:2.5.1.1 2.5.1.10]
            9453  GGPS1; geranylgeranyl diphosphate synthase 1 [KO:K00804] [EC:2.5.1.1 2.5.1.10 2.5.1.29]
            23590  PDSS1; decaprenyl diphosphate synthase subunit 1 [KO:K12504] [EC:2.5.1.91]
            57107  PDSS2; decaprenyl diphosphate synthase subunit 2 [KO:K12505] [EC:2.5.1.91]
            79947  DHDDS; dehydrodolichyl diphosphate synthase subunit [KO:K11778] [EC:2.5.1.87]
            116150  NUS1; NUS1 dehydrodolichyl diphosphate synthase subunit [KO:K19177] [EC:2.5.1.87]
            2339  FNTA; farnesyltransferase, CAAX box, alpha [KO:K05955] [EC:2.5.1.58 2.5.1.59]
            2342  FNTB; farnesyltransferase, CAAX box, beta [KO:K05954] [EC:2.5.1.58]
            100529261  CHURC1-FNTB; CHURC1-FNTB readthrough [KO:K05954] [EC:2.5.1.58]
            9986  RCE1; Ras converting CAAX endopeptidase 1 [KO:K08658] [EC:3.4.22.-]
            10269  ZMPSTE24; zinc metallopeptidase STE24 [KO:K06013] [EC:3.4.24.84]
            23463  ICMT; isoprenylcysteine carboxyl methyltransferase [KO:K00587] [EC:2.1.1.100]
            51449  PCYOX1; prenylcysteine oxidase 1 [KO:K05906] [EC:1.8.3.5 1.8.3.6]
COMPOUND    C00022  Pyruvate
            C00024  Acetyl-CoA
            C00118  D-Glyceraldehyde 3-phosphate
            C00129  Isopentenyl diphosphate
            C00235  Dimethylallyl diphosphate
            C00332  Acetoacetyl-CoA
            C00341  Geranyl diphosphate
            C00353  Geranylgeranyl diphosphate
            C00356  (S)-3-Hydroxy-3-methylglutaryl-CoA
            C00418  (R)-Mevalonate
            C00448  trans,trans-Farnesyl diphosphate
            C01107  (R)-5-Phosphomevalonate
            C01126  (2E,6E)-Farnesol
            C01143  (R)-5-Diphosphomevalonate
            C01230  all-trans-Hexaprenyl diphosphate
            C02321  cis-1,4-Polyisoprene
            C03461  2-trans,6-trans-Farnesal
            C04145  all-trans-Nonaprenyl diphosphate
            C04146  all-trans-Octaprenyl diphosphate
            C04216  all-trans-Heptaprenyl diphosphate
            C04506  Protein C-terminal S-farnesyl-L-cysteine
            C04574  di-trans,poly-cis-Undecaprenyl diphosphate
            C04748  Protein C-terminal S-farnesyl-L-cysteine methyl ester
            C05427  Phytyl diphosphate
            C05859  ditrans,polycis-Polyprenyl diphosphate
            C06081  Polyprenol
            C11434  2-C-Methyl-D-erythritol 4-phosphate
            C11435  4-(Cytidine 5'-diphospho)-2-C-methyl-D-erythritol
            C11436  2-Phospho-4-(cytidine 5'-diphospho)-2-C-methyl-D-erythritol
            C11437  1-Deoxy-D-xylulose 5-phosphate
            C11453  2-C-Methyl-D-erythritol 2,4-cyclodiphosphate
            C11811  1-Hydroxy-2-methyl-2-butenyl 4-diphosphate
            C16521  Isoprene
            C16826  2-cis,6-trans-Farnesyl diphosphate
            C17432  all-trans-Decaprenyl diphosphate
            C18321  trans,octacis-Decaprenyl diphosphate
            C19691  Farnesylcysteine
            C19760  2-cis,6-cis-Farnesyl diphosphate
            C19852  tritrans,heptacis-Undecaprenyl diphosphate
            C19853  trans,polycis-Polyprenyl diphosphate
            C20120  S-Farnesyl protein
            C20121  trans,trans-Farnesyl phosphate
            C20345  Isopentenyl phosphate
            C20847  (R)-Mevalonate 3-phosphate
            C20848  (R)-Mevalonate 3,5-bisphosphate
            C22453  trans-Anhydromevalonate phosphate
REFERENCE   PMID:12777052
  AUTHORS   Lange BM, Ghassemian M.
  TITLE     Genome organization in Arabidopsis thaliana: a survey for genes involved in isoprenoid and chlorophyll metabolism.
  JOURNAL   Plant Mol Biol 51:925-48 (2003)
            DOI:10.1023/A:1023005504702
REFERENCE   PMID:16262699
  AUTHORS   Saiki R, Nagata A, Kainou T, Matsuda H, Kawamukai M
  TITLE     Characterization of solanesyl and decaprenyl diphosphate synthases in mice and humans.
  JOURNAL   FEBS J 272:5606-22 (2005)
            DOI:10.1111/j.1742-4658.2005.04956.x
REFERENCE   PMID:9858571
  AUTHORS   Sato M, Sato K, Nishikawa S, Hirata A, Kato J, Nakano A
  TITLE     The yeast RER2 gene, identified by endoplasmic reticulum protein localization mutations, encodes cis-prenyltransferase, a key enzyme in dolichol synthesis.
  JOURNAL   Mol Cell Biol 19:471-83 (1999)
            DOI:10.1128/MCB.19.1.471
REFERENCE   PMID:24375100
  AUTHORS   Vannice JC, Skaff DA, Keightley A, Addo JK, Wyckoff GJ, Miziorko HM
  TITLE     Identification in Haloferax volcanii of phosphomevalonate decarboxylase and isopentenyl phosphate kinase as catalysts of the terminal enzyme reactions in an  archaeal alternate mevalonate pathway.
  JOURNAL   J Bacteriol 196:1055-63 (2014)
            DOI:10.1128/JB.01230-13
REL_PATHWAY hsa00010  Glycolysis / Gluconeogenesis
            hsa00100  Steroid biosynthesis
            hsa00130  Ubiquinone and other terpenoid-quinone biosynthesis
            hsa00270  Cysteine and methionine metabolism
            hsa00510  N-Glycan biosynthesis
KO_PATHWAY  ko00900
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