2.5.1.21 (2E,6E)-3,7,10-trimethylundeca-2,6-dienyl diphosphate + NADPH weak Sus scrofa diphosphate + ? - ? 323250 2.5.1.21 (2E,6E)-3,7,11-trimethyldodeca-2,6-dienyl diphosphate + NADPH - Sus scrofa diphosphate + ? - ? 323245 2.5.1.21 (2E,6E)-3,7,12-trimethyltrideca-2,6-dienyl diphosphate + NADPH weak Sus scrofa diphosphate + ? - ? 323251 2.5.1.21 (2E,6E)-3,7-dimethyldodeca-2,6-dienyl diphosphate + NADPH - Sus scrofa diphosphate + ? - ? 323246 2.5.1.21 (2E,6E)-3,7-dimethyltetradeca-2,6-dienyl diphosphate + NADPH weak Sus scrofa diphosphate + ? - ? 323249 2.5.1.21 (2E,6E)-3,7-dimethyltrideca-2,6-dienyl diphosphate + NADPH weak Sus scrofa diphosphate + ? - ? 323248 2.5.1.21 (2E,6E)-3,7-dimethylundeca-2,6-dienyl diphosphate + NADPH weak Sus scrofa diphosphate + ? - ? 323247 2.5.1.21 (2E,6E)-farnesyl diphosphate + NADH + H+ - Saccharomyces cerevisiae squalene + diphosphate + NAD+ - ? 452198 2.5.1.21 (2E,6E)-farnesyl diphosphate + NADPH + H+ - Tabernaemontana divaricata squalene + diphosphate + NADP+ - ? 452199 2.5.1.21 (E,E)-7-desmethylfarnesyl diphosphate + NADPH at 60% of the efficiency that farnesyl diphosphate is converted to squalene Saccharomyces cerevisiae 6,19-didesmethylsqualene + NADP+ + diphosphate in absence of farnesyl diphosphate, 6-desmethylsqualene is produced in presence of farnesyl diphosphate ? 323242 2.5.1.21 10,11-dihydrofarnesyl diphosphate + NADPH at 60% of the efficiency that farnesyl diphosphate is converted to squalene Saccharomyces cerevisiae 2,3,22,23-tetrahydrosqualene + NADP+ + diphosphate - ? 323241 2.5.1.21 2 (2E,6E)-farnesyl diphosphate - Homo sapiens diphosphate + presqualene diphosphate - ? 421775 2.5.1.21 2 (2E,6E)-farnesyl diphosphate - Withania somnifera diphosphate + presqualene diphosphate - ? 421775 2.5.1.21 2 (2E,6E)-farnesyl diphosphate first half-reaction Homo sapiens diphosphate + presqualene diphosphate - ? 421775 2.5.1.21 2 (2E,6E)-farnesyl diphosphate first reaction Populus trichocarpa diphosphate + presqualene diphosphate - ? 421775 2.5.1.21 2 (2E,6E)-farnesyl diphosphate first reaction Pinus massoniana diphosphate + presqualene diphosphate - ? 421775 2.5.1.21 2 (2E,6E)-farnesyl diphosphate + NAD(P)H + H+ - Chimonanthus salicifolius squalene + 2 diphosphate + NAD(P)+ - ? 457048 2.5.1.21 2 (2E,6E)-farnesyl diphosphate + NAD(P)H + H+ - Chimonanthus zhejiangensis squalene + 2 diphosphate + NAD(P)+ - ? 457048 2.5.1.21 2 (2E,6E)-farnesyl diphosphate + NAD(P)H + H+ - Chimonanthus grammatus squalene + 2 diphosphate + NAD(P)+ - ? 457048 2.5.1.21 2 (2E,6E)-farnesyl diphosphate + NAD(P)H + H+ overall reaction Chimonanthus salicifolius squalene + 2 diphosphate + NAD(P)+ - ? 457048 2.5.1.21 2 (2E,6E)-farnesyl diphosphate + NAD(P)H + H+ overall reaction Chimonanthus zhejiangensis squalene + 2 diphosphate + NAD(P)+ - ? 457048 2.5.1.21 2 (2E,6E)-farnesyl diphosphate + NAD(P)H + H+ overall reaction Chimonanthus grammatus squalene + 2 diphosphate + NAD(P)+ - ? 457048 2.5.1.21 2 (2E,6E)-farnesyl diphosphate + NADPH + H+ - Chlamydomonas reinhardtii squalene + 2 diphosphate + NADP+ - ? 421774 2.5.1.21 2 (2E,6E)-farnesyl diphosphate + NADPH + H+ - Botryococcus braunii squalene + 2 diphosphate + NADP+ - ? 421774 2.5.1.21 2 (2E,6E)-farnesyl diphosphate + NADPH + H+ - Thermosynechococcus vestitus squalene + 2 diphosphate + NADP+ - ? 421774 2.5.1.21 2 (2E,6E)-farnesyl diphosphate + NADPH + H+ - Homo sapiens squalene + 2 diphosphate + NADP+ - ? 421774 2.5.1.21 2 (2E,6E)-farnesyl diphosphate + NADPH + H+ - Withania somnifera squalene + 2 diphosphate + NADP+ - ? 421774 2.5.1.21 2 (2E,6E)-farnesyl diphosphate + NADPH + H+ - Methylococcus capsulatus squalene + 2 diphosphate + NADP+ - ? 421774 2.5.1.21 2 (2E,6E)-farnesyl diphosphate + NADPH + H+ - Mortierella alpina squalene + 2 diphosphate + NADP+ - ? 421774 2.5.1.21 2 (2E,6E)-farnesyl diphosphate + NADPH + H+ - Aurantiochytrium sp. KRS101 squalene + 2 diphosphate + NADP+ - ? 421774 2.5.1.21 2 (2E,6E)-farnesyl diphosphate + NADPH + H+ - Candida tropicalis squalene + 2 diphosphate + NADP+ - ? 421774 2.5.1.21 2 (2E,6E)-farnesyl diphosphate + NADPH + H+ - Populus trichocarpa squalene + 2 diphosphate + NADP+ - ? 421774 2.5.1.21 2 (2E,6E)-farnesyl diphosphate + NADPH + H+ - Pinus massoniana squalene + 2 diphosphate + NADP+ - ? 421774 2.5.1.21 2 (2E,6E)-farnesyl diphosphate + NADPH + H+ - Rattus norvegicus squalene + 2 diphosphate + NADP+ - ? 421774 2.5.1.21 2 (2E,6E)-farnesyl diphosphate + NADPH + H+ - Aspergillus flavus squalene + 2 diphosphate + NADP+ - ? 421774 2.5.1.21 2 (2E,6E)-farnesyl diphosphate + NADPH + H+ - Siraitia grosvenorii squalene + 2 diphosphate + NADP+ - ? 421774 2.5.1.21 2 (2E,6E)-farnesyl diphosphate + NADPH + H+ overall reaction Homo sapiens squalene + 2 diphosphate + NADP+ - ? 421774 2.5.1.21 2 (2E,6E)-farnesyl diphosphate + NADPH + H+ overall reaction Panax notoginseng squalene + 2 diphosphate + NADP+ - ? 421774 2.5.1.21 2 (2E,6E)-farnesyl diphosphate + NADPH + H+ overall reaction Solanum tuberosum squalene + 2 diphosphate + NADP+ - ? 421774 2.5.1.21 2 (2E,6E)-farnesyl diphosphate + NADPH + H+ overall reaction Leishmania donovani squalene + 2 diphosphate + NADP+ - ? 421774 2.5.1.21 2 (2E,6E)-farnesyl diphosphate + NADPH + H+ overall reaction Withania somnifera squalene + 2 diphosphate + NADP+ - ? 421774 2.5.1.21 2 (2E,6E)-farnesyl diphosphate + NADPH + H+ overall reaction Salvia miltiorrhiza squalene + 2 diphosphate + NADP+ - ? 421774 2.5.1.21 2 (2E,6E)-farnesyl diphosphate + NADPH + H+ overall reaction Tripterygium wilfordii squalene + 2 diphosphate + NADP+ - ? 421774 2.5.1.21 2 (2E,6E)-farnesyl diphosphate + NADPH + H+ overall reaction Aspergillus flavus squalene + 2 diphosphate + NADP+ - ? 421774 2.5.1.21 2 (2E,6E)-farnesyl diphosphate + NADPH + H+ farnesyl diphosphate forms hydrogen bonds with enzyme residues Arg49, Arg74, Ser48, and Val47 of conserved 77DTVED81 motif Pinus massoniana squalene + 2 diphosphate + NADP+ - ? 421774 2.5.1.21 2 (2E,6E)-farnesyl diphosphate + NADPH + H+ farnesyl diphosphate forms hydrogen bonds with enzyme residues Asp81, Asp217, Glu80, and Gln206 of conserved 77DTVED81 and 213DYLED217 motifs Populus trichocarpa squalene + 2 diphosphate + NADP+ - ? 421774 2.5.1.21 2 (2E,6E)-farnesyl diphosphate + NADPH + H+ overall reaction, the enzyme catalyzes the two-step reductive head-to-head condensation of two molecules of farnesyl pyrophosphate to form squalene using presqualene diphosphate (PSPP) as an intermediate Homo sapiens squalene + 2 diphosphate + NADP+ - ? 421774 2.5.1.21 2 (2E,6E)-farnesyl diphosphate + NADPH + H+ specific for, the enzyme catalyzes a head-to-head condensation reaction (1'-2,3-linked) between two molecules of farnesyl diphosphate (C15) forms a cyclopropylcarbinyl intermediate, presqualene diphosphate. The subsequent conversion of presqualene diphosphate to squalene involves an extensive rearrangement of the carbon skeleton and an NADPH-dependent reduction reaction Methylococcus capsulatus squalene + 2 diphosphate + NADP+ - ? 421774 2.5.1.21 2 (2E,6E)-farnesyl diphosphate + NADPH + H+ the enzyme initially catalyzes the condensation of two molecules of farnesyl diphosphate (FPP) to form presqualene diphosphate (PSPP), and next converting PSPP to squalene in a reaction requiring NADPH and Mg2+ Aurantiochytrium sp. KRS101 squalene + 2 diphosphate + NADP+ product analysis by GC-MS analysis ? 421774 2.5.1.21 2 (2E,6E)-farnesyl diphosphate + NADPH + H+ squalene synthase catalyzes the first enzymatic step from the central isoprenoid pathway toward sterol and triterpenoid biosynthesis Panax notoginseng squalene + 2 diphosphate + NADP+ - ? 421774 2.5.1.21 2 (2E,6E)-farnesyl diphosphate + NADPH + H+ the enzyme catalyzes the first dedicated step in the biosynthesis of sterols and other triterpenoids Salvia miltiorrhiza squalene + 2 diphosphate + NADP+ - ? 421774 2.5.1.21 2 (2E,6E)-farnesyl diphosphate + NADPH + H+ the enzyme is involved in celastrol biosynthesis Tripterygium wilfordii squalene + 2 diphosphate + NADP+ - ? 421774 2.5.1.21 2 (2E,6E)-farnesyl diphosphate + NADPH + H+ - Mortierella alpina ATCC 32222 squalene + 2 diphosphate + NADP+ - ? 421774 2.5.1.21 2 (2E,6E)-farnesyl diphosphate + NADPH + H+ overall reaction Leishmania donovani MHOM/IN/80/Dd8 squalene + 2 diphosphate + NADP+ - ? 421774 2.5.1.21 2 (2E,6E)-farnesyl diphosphate + NADPH + H+ - Aspergillus flavus AF70 squalene + 2 diphosphate + NADP+ - ? 421774 2.5.1.21 2 (2E,6E)-farnesyl diphosphate + NADPH + H+ overall reaction Aspergillus flavus AF70 squalene + 2 diphosphate + NADP+ - ? 421774 2.5.1.21 2 (2E,6E)-farnesyl diphosphate + NADPH + H+ - Candida tropicalis ATCC MYA-3404 squalene + 2 diphosphate + NADP+ - ? 421774 2.5.1.21 2 (2E,6E)-farnesyl diphosphate + NADPH + H+ overall reaction Solanum tuberosum Desiree squalene + 2 diphosphate + NADP+ - ? 421774 2.5.1.21 2 farnesyl diphosphate - Cavia porcellus presqualene diphosphate + diphosphate - ? 397163 2.5.1.21 2 farnesyl diphosphate - Mus musculus presqualene diphosphate + diphosphate - ? 397163 2.5.1.21 2 farnesyl diphosphate - Homo sapiens presqualene diphosphate + diphosphate - ? 397163 2.5.1.21 2 farnesyl diphosphate - Rattus norvegicus presqualene diphosphate + diphosphate - ? 397163 2.5.1.21 2 farnesyl diphosphate - Oryctolagus cuniculus presqualene diphosphate + diphosphate - ? 397163 2.5.1.21 2 farnesyl diphosphate - Macaca mulatta presqualene diphosphate + diphosphate - ? 397163 2.5.1.21 2 farnesyl diphosphate - Euphorbia tirucalli presqualene diphosphate + diphosphate - ? 397163 2.5.1.21 2 farnesyl diphosphate - Thermosynechococcus vestitus presqualene diphosphate + diphosphate in absence of NADPH, formation of presqualene diphosphate ? 397163 2.5.1.21 2 farnesyl diphosphate assay at pH 7.2, 30°C, 3 h Saccharomyces cerevisiae presqualene diphosphate + diphosphate - ? 397163 2.5.1.21 2 farnesyl diphosphate + NADPH + H+ - Botryococcus braunii squalene + 2 diphosphate + NADP+ - ? 461439 2.5.1.21 2-methylfarnesyl diphosphate + NADPH - Rattus norvegicus 11-methylsqualene + NADP+ + diphosphate - ? 323243 2.5.1.21 2-methylfarnesyl diphosphate + NADPH - Saccharomyces cerevisiae 11-methylsqualene + NADP+ + diphosphate - ? 323243 2.5.1.21 3-demethylfarnesyl diphosphate + NADPH - Rattus norvegicus 10-demethylsqualene + NADP+ + diphosphate - ? 323244 2.5.1.21 3-demethylfarnesyl diphosphate + NADPH - Saccharomyces cerevisiae 10-demethylsqualene + NADP+ + diphosphate - ? 323244 2.5.1.21 farnesyl diphosphate - Sus scrofa 12,13-cis-dehydrosqualene + diphosphate - ? 323240 2.5.1.21 farnesyl diphosphate - Saccharomyces cerevisiae 12,13-cis-dehydrosqualene + diphosphate - ? 323240 2.5.1.21 farnesyl diphosphate in presence of Mn2+ Saccharomyces cerevisiae 12,13-cis-dehydrosqualene + diphosphate 12-cis-dehydrosqualene + diphosphate ? 323240 2.5.1.21 farnesyl diphosphate + farnesyl diphosphate - Homo sapiens diphosphate + presqualene diphosphate - ? 323237 2.5.1.21 farnesyl diphosphate + farnesyl diphosphate - Rattus norvegicus diphosphate + presqualene diphosphate - ? 323237 2.5.1.21 farnesyl diphosphate + farnesyl diphosphate - Saccharomyces cerevisiae diphosphate + presqualene diphosphate - ? 323237 2.5.1.21 farnesyl diphosphate + farnesyl diphosphate first pathway-specific enzyme in cholesterol biosynthesis Saccharomyces cerevisiae diphosphate + presqualene diphosphate - ? 323237 2.5.1.21 farnesyl diphosphate + farnesyl diphosphate first pathway-specific enzyme in cholesterol biosynthesis Nicotiana tabacum diphosphate + presqualene diphosphate - ? 323237 2.5.1.21 farnesyl diphosphate + farnesyl diphosphate squalene is the first sterol intermediate in cholesterol biosynthesis Rattus norvegicus diphosphate + presqualene diphosphate - ? 323237 2.5.1.21 farnesyl diphosphate + farnesyl diphosphate essential enzyme in cholesterol biosynthetic pathway Saccharomyces cerevisiae diphosphate + presqualene diphosphate - ? 323237 2.5.1.21 farnesyl diphosphate + farnesyl diphosphate enzyme may be important during response to infection and inflammation Homo sapiens diphosphate + presqualene diphosphate - ? 323237 2.5.1.21 farnesyl diphosphate + farnesyl diphosphate enzyme may be important during response to infection and inflammation Rattus norvegicus diphosphate + presqualene diphosphate - ? 323237 2.5.1.21 farnesyl diphosphate + NAD(P)H - Rattus norvegicus squalene + diphosphate + NAD(P)+ - ? 323239 2.5.1.21 farnesyl diphosphate + NAD(P)H - Sus scrofa squalene + diphosphate + NAD(P)+ - ? 323239 2.5.1.21 farnesyl diphosphate + NAD(P)H - Saccharomyces cerevisiae squalene + diphosphate + NAD(P)+ - ? 323239 2.5.1.21 farnesyl diphosphate + NAD(P)H - Nicotiana tabacum squalene + diphosphate + NAD(P)+ - ? 323239 2.5.1.21 farnesyl diphosphate + NAD(P)H - Narcissus pseudonarcissus squalene + diphosphate + NAD(P)+ - ? 323239 2.5.1.21 farnesyl diphosphate + NAD(P)H - Saccharomyces cerevisiae squalene + diphosphate + NAD(P)+ presqualene diphosphate and squalene are produced in a ratio of 6:1 ? 323239 2.5.1.21 farnesyl diphosphate + NAD(P)H + H+ - Homo sapiens squalene + diphosphate + NAD(P)+ - ? 388676 2.5.1.21 farnesyl diphosphate + NAD(P)H + H+ - Trypanosoma cruzi squalene + diphosphate + NAD(P)+ - ? 388676 2.5.1.21 farnesyl diphosphate + NADPH + H+ - Thermosynechococcus vestitus squalene + diphosphate + NADP+ sole product ? 397158 2.5.1.21 additional information specificity overview Rattus norvegicus ? - ? 89 2.5.1.21 additional information specificity overview Sus scrofa ? - ? 89 2.5.1.21 additional information specificity overview Saccharomyces cerevisiae ? - ? 89 2.5.1.21 additional information none of the following analogues gives nonpolar products: 7,11-dimethyl-3-ethyl-2,6,10-dodecatrienyl diphosphate, 6,7,10,11-tetrahydrofarnesyl diphosphate, 4-methylthiofarnesyl diphosphate, 4-fluorofarnesyl diphosphate Rattus norvegicus ? - ? 89 2.5.1.21 additional information none of the following analogues gives nonpolar products: 7,11-dimethyl-3-ethyl-2,6,10-dodecatrienyl diphosphate, 6,7,10,11-tetrahydrofarnesyl diphosphate, 4-methylthiofarnesyl diphosphate, 4-fluorofarnesyl diphosphate Saccharomyces cerevisiae ? - ? 89 2.5.1.21 additional information reaction is completely regioselective Saccharomyces cerevisiae ? - ? 89 2.5.1.21 additional information replacement of 3-methyl of farnesyl diphosphate by an ethyl group or introduction of a methyl group at C-4 results in a complete loss of activity Sus scrofa ? - ? 89 2.5.1.21 additional information no substrate: 6,7-dihydrofarnesyl diphosphate, 3-desmethylfarnesyl diphosphate Saccharomyces cerevisiae ? - ? 89 2.5.1.21 additional information not metabolized: (E)-6,7,10,11-tetrahydrofarnesyl diphosphate Saccharomyces cerevisiae ? - ? 89 2.5.1.21 additional information enzyme is key regulator not only for phytosterol but also for triterpene biosynthesis Panax ginseng ? - ? 89 2.5.1.21 additional information the catalytic process involves two reactions: firstly, two FPP molecules are condensed to form presqualene diphosphate (PSPP), an intermediate with a cyclopropane C1'-C2-C3 ring structure, and secondly, PSPP undergoes a NADPH-dependent rearrangement and reduction to generate the end product squalene Homo sapiens ? - ? 89 2.5.1.21 additional information catalytic mechanism, overview Homo sapiens ? - ? 89 2.5.1.21 additional information squalene and botryococcene are branched-chain, triterpene compounds that arise from the head-to-head condensation of two molecules of farnesyl diphosphate to yield 1'-1 and 1'-3 linkages, respectively. Different enzymes are responsible for botryococcene and squalene biosynthesis in the green alga Botryococcus braunii race B. The specificity for the 1'-1 and 1'-3 linkages is controlled by residues in the active sites that can mediate catalytic specificity. Identification of several amino acid positions contributing to the rearrangement of the cyclopropyl intermediate to squalene, The same positions do not appear to be sufficient to account for the cyclopropyl rearrangement to give botryococcene, oerview Botryococcus braunii ? - ? 89 2.5.1.21 additional information analysis of substrate specificity, overview Botryococcus braunii ? - ? 89 2.5.1.21 presqualene diphosphate + NAD(P)H - Rattus norvegicus squalene + NAD(P)+ + diphosphate - ? 323238 2.5.1.21 presqualene diphosphate + NAD(P)H - Saccharomyces cerevisiae squalene + NAD(P)+ + diphosphate - ? 323238 2.5.1.21 presqualene diphosphate + NAD(P)H in presence of reducing pyridine nucleotide, preferably NADPH, squalene is formed, in absence of reducing cofactor the rate of the condensation reaction is lower and all of the product accumulates as presqualene diphosphate Rattus norvegicus squalene + NAD(P)+ + diphosphate - ? 323238 2.5.1.21 presqualene diphosphate + NAD(P)H in presence of reducing pyridine nucleotide, preferably NADPH, squalene is formed, in absence of reducing cofactor the rate of the condensation reaction is lower and all of the product accumulates as presqualene diphosphate Sus scrofa squalene + NAD(P)+ + diphosphate - ? 323238 2.5.1.21 presqualene diphosphate + NAD(P)H in presence of reducing pyridine nucleotide, preferably NADPH, squalene is formed, in absence of reducing cofactor the rate of the condensation reaction is lower and all of the product accumulates as presqualene diphosphate Saccharomyces cerevisiae squalene + NAD(P)+ + diphosphate - ? 323238 2.5.1.21 presqualene diphosphate + NAD(P)H presqualene diphosphate synthetase and squalene synthetase are copurified during isolation Saccharomyces cerevisiae squalene + NAD(P)+ + diphosphate - ? 323238 2.5.1.21 presqualene diphosphate + NAD(P)H a single active site catalyzes both reactions Saccharomyces cerevisiae squalene + NAD(P)+ + diphosphate - ? 323238 2.5.1.21 presqualene diphosphate + NAD(P)H one protein with 2 catalytic sites may be involved in synthesis of presqualene diphosphate and for its reduction to squalene Saccharomyces cerevisiae squalene + NAD(P)+ + diphosphate - ? 323238 2.5.1.21 presqualene diphosphate + NAD(P)H the polymeric form of the enzyme also catalyzes the reduction of presqualene diphosphate by NADPH to squalene Saccharomyces cerevisiae squalene + NAD(P)+ + diphosphate - ? 323238 2.5.1.21 presqualene diphosphate + NAD(P)H + H+ - Cavia porcellus squalene + diphosphate + NAD(P)+ - ? 407296 2.5.1.21 presqualene diphosphate + NAD(P)H + H+ - Mus musculus squalene + diphosphate + NAD(P)+ - ? 407296 2.5.1.21 presqualene diphosphate + NAD(P)H + H+ - Homo sapiens squalene + diphosphate + NAD(P)+ - ? 407296 2.5.1.21 presqualene diphosphate + NAD(P)H + H+ - Rattus norvegicus squalene + diphosphate + NAD(P)+ - ? 407296 2.5.1.21 presqualene diphosphate + NAD(P)H + H+ - Macaca mulatta squalene + diphosphate + NAD(P)+ - ? 407296 2.5.1.21 presqualene diphosphate + NAD(P)H + H+ - Euphorbia tirucalli squalene + diphosphate + NAD(P)+ - ? 407296 2.5.1.21 presqualene diphosphate + NAD(P)H + H+ second reaction Populus trichocarpa squalene + diphosphate + NAD(P)+ - ? 407296 2.5.1.21 presqualene diphosphate + NAD(P)H + H+ second reaction Pinus massoniana squalene + diphosphate + NAD(P)+ - ? 407296 2.5.1.21 presqualene diphosphate + NADPH + H+ - Homo sapiens squalene + diphosphate + NADP+ - ? 407297 2.5.1.21 presqualene diphosphate + NADPH + H+ - Oryctolagus cuniculus squalene + diphosphate + NADP+ - ? 407297 2.5.1.21 presqualene diphosphate + NADPH + H+ - Botryococcus braunii squalene + diphosphate + NADP+ - ? 407297 2.5.1.21 presqualene diphosphate + NADPH + H+ - Withania somnifera squalene + diphosphate + NADP+ - ? 407297 2.5.1.21 presqualene diphosphate + NADPH + H+ second half reaction Homo sapiens squalene + diphosphate + NADP+ - ? 407297