Farnesyl pyrophosphate synthase (FDPS) (FDPS)

Farnesyl pyrophosphate synthase (FDPS) is a key enzyme in the mevalonate pathway, catalyzing the production of farnesyl pyrophosphate (FPP) from isopentenyl pyrophosphate and dimethylallyl pyrophosphate (UniProt: P14324). FPP is a vital precursor for the synthesis of cholesterol, ubiquinone, and dolichol, and it is essential for the post-translational prenylation of small GTPases like Ras, Rho, and Rab. These GTPases regulate key cellular processes, including vesicle trafficking, cytoskeletal organization, and cell survival. FDPS is the primary pharmacological target of nitrogen-containing bisphosphonates, which are the gold standard treatment for metabolic bone diseases such as osteoporosis and Paget's disease (PubMed: 11566450). By inhibiting FDPS, these drugs disrupt the prenylation of proteins necessary for osteoclast activity, leading to the inactivation and apoptosis of these bone-resorbing cells. Additionally, FDPS is under investigation as a target for anticancer therapies and certain parasitic infections due to its central role in cellular metabolism and signaling (PubMed: 21605000). Therapeutic challenges include potential side effects like osteonecrosis of the jaw and atypical fractures, which may arise from long-term suppression of bone turnover.

Other names

Farnesyl diphosphate synthaseGeranyltranstransferaseDimethylallyltranstransferaseFPPSFPS

Inhibition of farnesyl pyrophosphate synthase (FDPS) in the mevalonate pathway, which prevents the formation of farnesyl pyrophosphate and geranylgeranyl pyrophosphate. This depletion inhibits the post-translational prenylation of small GTP-binding proteins (e.g., Ras, Rho, Rab) essential for osteoclast function, leading to osteoclast inactivation and apoptosis (PubMed: 11566450, 21605000).