Alendronate: Difference between revisions

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<scene name='Sandbox_59/Fpps/2'>FPPS</scene> is considered the main target protein of aminobisphosphonates (including alendronate). FPPS is the prenyl transferase in the HMG-CoA Reductase Pathway, which forms cholesterol (sterols and terpenoids) from acetyl CoA. It reacts with 3-isopentenyl pyrophosphate (IPP) to form geranyl pyrophosphate (GGP). Researchers discovered that alendronate inhibits FPPS because they found a build-up of IPP in the cell, but less GGP.<ref>http://www.ncbi.nlm.nih.gov/pubmed/10620343</ref>

<scene name='Sandbox_59/Fpps/3'>Farnesyl pyrophosphate synthase (FPPS)</scene> is considered the main target protein of aminobisphosphonates (including alendronate). FPPS is the prenyl transferase in the HMG-CoA Reductase Pathway, which forms cholesterol (sterols and terpenoids) from acetyl CoA. It reacts with 3-isopentenyl pyrophosphate (IPP) to form geranyl pyrophosphate (GGP). Researchers discovered that alendronate inhibits FPPS because they found a build-up of IPP in the cell, but less GGP.<ref>http://www.ncbi.nlm.nih.gov/pubmed/10620343</ref>

The identified mechanism of alendronate on FPPS begins with the absorption of the alendronate into the osteoclast via binding to hydroxyapatite. Once in the osteoclast, the <scene name='Sandbox_59/Active_site_ligand_space_fill/2'>alendronate binds</scene> to the active site of FPPS.<ref>Fisher et. all. ''Alendronate mechanism of action: geranylgeraniol, an intermediate in the mevalonate pathway, prevents inhibition of osteoclast formation, bone resorption, and kinase activation in vitro''.Cell Biology, Vol. 96, pp. 133–138, January 1999</ref> In the active site, it appears that the alendronate interacts directly with <scene name='Sandbox_59/Active_site_ligand/2'>three Asp residues</scene>, not allowing the IPP to bind, and effectively daectivating FPPS.

Alendronate: Difference between revisions

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 <Structure load='2f92' size='450' frame='true' align='right' caption='Shown: The asymmetric subunit of FPPS, not the assumed biological molecule.' scene='Insert optional scene name here' />
-<scene name='Sandbox_59/Fpps/2'>FPPS</scene> is considered the main target protein of aminobisphosphonates (including alendronate). FPPS is the prenyl transferase in the HMG-CoA Reductase Pathway, which forms cholesterol (sterols and terpenoids) from acetyl CoA. It reacts with 3-isopentenyl pyrophosphate (IPP) to form geranyl pyrophosphate (GGP). Researchers discovered that alendronate inhibits FPPS because they found a build-up of IPP in the cell, but less GGP.<ref>http://www.ncbi.nlm.nih.gov/pubmed/10620343</ref>
+<scene name='Sandbox_59/Fpps/3'>Farnesyl pyrophosphate synthase (FPPS)</scene> is considered the main target protein of aminobisphosphonates (including alendronate). FPPS is the prenyl transferase in the HMG-CoA Reductase Pathway, which forms cholesterol (sterols and terpenoids) from acetyl CoA. It reacts with 3-isopentenyl pyrophosphate (IPP) to form geranyl pyrophosphate (GGP). Researchers discovered that alendronate inhibits FPPS because they found a build-up of IPP in the cell, but less GGP.<ref>http://www.ncbi.nlm.nih.gov/pubmed/10620343</ref>
 The identified mechanism of alendronate on FPPS begins with the absorption of the alendronate into the osteoclast via binding to hydroxyapatite. Once in the osteoclast, the <scene name='Sandbox_59/Active_site_ligand_space_fill/2'>alendronate binds</scene> to the active site of FPPS.<ref>Fisher et. all. ''Alendronate mechanism of action: geranylgeraniol, an intermediate in the mevalonate pathway, prevents inhibition of osteoclast formation, bone resorption, and kinase activation in vitro''.Cell Biology, Vol. 96, pp. 133–138, January 1999</ref> In the active site, it appears that the alendronate interacts directly with <scene name='Sandbox_59/Active_site_ligand/2'>three Asp residues</scene>, not allowing the IPP to bind, and effectively daectivating FPPS.