Methylenebisphosphonate and triphosphate derivatives of the mevalonate pathway are substrates of yeast UTP:glucose-1-phosphate uridylyltransferase

UTP:glucose-1-phospate uridylyltransferase (EC 2.7.7.9) from Saccharomyces cerevisiae transfers the uridylyl moiety of UDP-glucose onto methylenebisphosphonate (pCH2p) yielding uridine 5′-(β,γ-methylenetriphosphate) (UppCH2p). 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 Km (mM) and Vmax (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 Km and Vmax values for methylenebisphosphonate were 1.1 ± 0.2 mM and 4055 ± 96 mU/mg protein, respectively. ► Uridylyltransferase transfers UMP to the bisphosphonate pCH2p forming UppCH2p. ► This enzyme forms UppppMev from triphosphate derivatives of mevalonate(Mev). ► Connections with the effect of bisphosphonates on osteoporosis are suggested.