Inhibition of Farnesyl and Geranylgeranyl Diphosphate Synthases

Sarah A. Holstein, Raymond J. Hohl

Research output: Chapter in Book/Report/Conference proceedingChapter

6 Scopus citations


The prenyl diphosphate synthases, farnesyl diphosphate synthase (FDPS), and geranylgeranyl diphosphate synthase (GGDPS) are responsible for the production of two key isoprenoids farnesyl diphosphate (FPP) and geranylgeranyl disphosphate (GGPP). Not only do these isoprenoid diphosphates serve as precursors for other isoprenoids, but they are also the lipid donors for protein prenylation reactions. The nitrogenous bisphosphonates (NBPs) are inhibitors of FDPS and are widely used clinically in the management of a variety of bony disorders including osteoporosis and metastatic bone disease. The mechanism of action underlying their effects on osteoclasts appears to be predominantly related to their ability to diminish protein prenylation. Of increasing interest is the development of specific GGDPS inhibitors. Here, we discuss the use of FDPS and GGDPS inhibitors as an alternative strategy with which to impair protein prenylation and to disrupt isoprenoid homeostasis.

Original languageEnglish (US)
Title of host publicationEnzymes
PublisherAcademic Press
Number of pages19
StatePublished - 2011
Externally publishedYes

Publication series

ISSN (Print)1874-6047


  • Bisphosphonates
  • Farnesyl diphosphate synthase
  • Farnesyl diphosphate synthase inhibitors
  • Geranylgeranyl diphosphate synthase
  • Geranylgeranyl diphosphate synthase inhibitors
  • Isoprenoid biosynthetic pathway
  • Nitrogenous bisphosphonates
  • Prenyl diphosphate synthases
  • Single nucleotide polymorphisms

ASJC Scopus subject areas

  • Biotechnology
  • Biophysics
  • Biochemistry
  • Molecular Biology


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