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

Biochimie. 2012 Sep;94(9):1871-5. doi: 10.1016/j.biochi.2012.04.022. Epub 2012 May 2.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biocatalysis
  • Diphosphonates / metabolism*
  • Mevalonic Acid / analogs & derivatives
  • Mevalonic Acid / metabolism*
  • Phosphorylation
  • Polyphosphates / metabolism*
  • Protein Binding
  • Saccharomyces cerevisiae / enzymology*
  • Substrate Specificity
  • UTP-Glucose-1-Phosphate Uridylyltransferase / metabolism*
  • Uridine Monophosphate / metabolism

Substances

  • Diphosphonates
  • Polyphosphates
  • Uridine Monophosphate
  • UTP-Glucose-1-Phosphate Uridylyltransferase
  • triphosphoric acid
  • Mevalonic Acid