title: Methylenebisphosphonate and triphosphate derivatives of the mevalonate pathway are substrates of yeast UTP:glucose-1-phosphate uridylyltransferase.
abstract: UTP:glucose-1-phospate uridylyltransferase (EC 2.7.7.9) from Saccharomyces cerevisiae transfers the uridylyl moiety of UDP-glucose onto methylenebisphosphonate (pCH(2)p) yielding uridine 5'-(β,γ-methylenetriphosphate) (UppCH(2)p). The following bisphosphonates were not acceptors of UMP: alendronate, pamidronate, clodronate and etidronate. UDP-glucose serves as uridylyl donor to triphosphate derivatives of the mevalonate pathway: farnesyl (far-PPP), geranyl (ger-PPP) and isopentenyl (iso-PPP), with formation of farnesyl-tetraphosphouridine (far-ppppU); geranyl-tetraphosphouridine (ger-ppppU) and isopentenyl-tetraphosphouridine (iso-ppppU). The K(m) (mM) and V(max) (mU/mg protein) values determined for these substrates were: 0.32 ± 0.07 and 4.9 ± 0.6; 0.21 ± 0.06 and 5.7 ± 0.8; 0.51 ± 0.14 and 2.0 ± 0.2, respectively. The K(m) and V(max) values for methylenebisphosphonate were 1.1 ± 0.2 mM and 4055 ± 96 mU/mg protein, respectively.
authors.affiliation: Departamento de Bioquímica, Instituto de Investigaciones Biomédicas Alberto Sols, UAM/CSIC, Facultad de Medicina, 28029 Madrid, Spain.
authors.forename: María Antonia
authors.initials: MA
authors.lastname: Günther Sillero
authors.forename: Anabel
authors.initials: A
authors.lastname: de Diego
authors.forename: Antonio
authors.initials: A
authors.lastname: Sillero
mesh_terms: D055162:Biocatalysis; D004164:Diphosphonates / Q000378:metabolism*; D008798:Mevalonic Acid / Q000031:analogs & derivatives / Q000378:metabolism*; D010766:Phosphorylation; D011122:Polyphosphates / Q000378:metabolism*; D011485:Protein Binding; D012441:Saccharomyces cerevisiae / Q000201:enzymology*; D013379:Substrate Specificity; D005957:UTP-Glucose-1-Phosphate Uridylyltransferase / Q000378:metabolism*; D014542:Uridine Monophosphate / Q000378:metabolism
chemical_list: D004164:Diphosphonates; D011122:Polyphosphates; D014542:Uridine Monophosphate; D005957:UTP-Glucose-1-Phosphate Uridylyltransferase; C005692:triphosphoric acid; D008798:Mevalonic Acid