Alendronate: Difference between revisions
From Proteopedia
Jump to navigationJump to search
No edit summary |
No edit summary |
||
| Line 18: | Line 18: | ||
Alendronate is an aminobisphosphonate with a nonhydrolyzable P-C-P. Alendronate generally affects the activity of osteoclasts in bone. Osteoclasts are responsible for breaking down bone and also for bone resorption (losing bone substance). <ref>http://www.medterms.com/script/main/art.asp?articlekey=11794</ref> When alendronate is present, bone resorption is inhibited and bone breakdown is diminished. | Alendronate is an aminobisphosphonate with a nonhydrolyzable P-C-P. Alendronate generally affects the activity of osteoclasts in bone. Osteoclasts are responsible for breaking down bone and also for bone resorption (losing bone substance). <ref>http://www.medterms.com/script/main/art.asp?articlekey=11794</ref> When alendronate is present, bone resorption is inhibited and bone breakdown is diminished. | ||
== Target Proteins and Bone == | == Target Proteins and Bone == | ||
| Line 33: | Line 32: | ||
<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' /> | <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). | <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. | ||
The identified mechanism of alendronate on FPPS begins with the absorption of the alendronate into the osteoclast. 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> | |||
<scene name='Sandbox_59/ | |||
<scene name='Sandbox_59/Active_site_ligand_space_fill/2'>alendronate binds</scene> | |||
<scene name='Sandbox_59/Active_site_ligand/2'>active site bound sticks</scene> | |||
<scene name='Sandbox_59/Fpps_bound_phosphate/2'>FPPS bound phosphate</scene> | <scene name='Sandbox_59/Fpps_bound_phosphate/2'>FPPS bound phosphate</scene> | ||
