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Pathway Description
Zoledronate Action Pathway
Homo sapiens
Drug Action Pathway
Zoledronate (also named zoledronic acid, Zometa or Reclast) is a type of medication that used to treat numbers of bone diseases because of its affinity for hydroxyapatite. Zoledronate targets farnesyl pyrophosphate (FPP) synthase by inhibiting the function of this enzyme in the mevalonate pathway, which prevent the biosynthesis of Geranyl-PP and farnesyl pyrophosphate. Geranyl-PP and farnesyl pyrophosphate are important for geranylgeranylation and farnesylation of GTPase signalling proteins. Lack of Geranyl-PP and farnesyl pyrophosphate will result in decreased rate of bond resorption and turnover as well as block the osteoclast activity, which lead to an increasing mass gain in bone (i.e. net gain in bone mass).
References
Zoledronate Pathway References
Reszka AA, Rodan GA: Bisphosphonate mechanism of action. Curr Rheumatol Rep. 2003 Feb;5(1):65-74.
Pubmed: 12590887
Seibel, M.J. Bone metabolism. In S. Offermanns, & W. Rosenthal (Eds.). Encyclopedic reference of molecular pharmacology. 2004;190-197. Berlin, Germany: Springer.
Steroid Biosynthesis References
Lehninger, A.L. Lehninger principles of biochemistry (4th ed.) (2005). New York: W.H Freeman.
Norman, A.W, and Litwack, G. Hormones (2nd ed.) (1997) San Diego : Academic Press.
Salway, J.G. Metabolism at a glance (3rd ed.) (2004). Alden, Mass.: Blackwell Pub.
Vance, D.E., and Vance, J.E. Biochemistry of lipids, lipoproteins, and membranes (4th ed.) (2002) Amsterdam; Boston: Elsevier.
Simons J: The $10 billion pill. Fortune. 2003 Jan 20;147(1):58-62, 66, 68.
Pubmed: 12602122
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