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Farnesyl pyrophosphate synthase Farnesyl pyrophosphate synthase HMG-CoA reductase Mevalonate kinase Phosphomevalonate kinase Squalene synthase Diphosphomevalonate decarboxylase Geranylgeranyl pyrophosphate synthase Hydroxymethylglutaryl- CoA synthase, cytoplasmic Acetyl-CoA acetyltransferase, mitochondrial Alendronate Alendronate Alendronate Alendronate Alendronate 3-Hydroxy-3-methylglutaryl-CoA NADPH H+ NADP CoA Mevalonate ATP Mevalonate-5P ADP ATP Mevalonate-5PP ADP Isopentenyl-PP Dimethylallylpyrophosphate PPi Geranyl-PP Isopentenyl pyrophosphate Farnesyl pyrophosphate PPi H+ NADPH PPi NADP Squalene Cholesterol ATP ADP Pi CO2 Isopentenyl pyrophosphate Geranylgeranyl-PP PPi Acetyl-CoA H2O Acetoacetyl-CoA CoA CoA Magnesium Magnesium Magnesium Magnesium Osteoclast Cytosol Alendronate enters the cell through endocytosis. The endocytic vesicles are acidified and the alendronate is released into the cytosol. Alendronate inhibit farnesyl pyrophosphate by binding in it's active site. Reduced production of farnesyl-PP, geranylgernayl-PP and other sterols which are essential for anchoring cell surface protein via prenylation, and are necessary for osteoclast function and survival. Low concentrations of these lipids prevents osteoclast attachment to the bone, thereby inducing apoptosis of the osteoclast, reducing osteoclast activity and bone resorption. Mevalonate Pathway Bone Loss Alendronate is administered orally and travels to the bone Alendronate acts to counteract osteoclast activity and reduce bone degradation
FDPS FDPS HMGCLL1 MVK PMVK FDFT1 MVD GGPS1 HMGCS1 ACAT1 Alendronate Alendronate Alendronate Alendronate Alendronate 3-Hydroxy-3- methylglutaryl- CoA NADPH Hydrogen Ion NADP Coenzyme A Mevalonate Adenosine triphosphate Mevalonate-5P Adenosine diphosphate Adenosine triphosphate Mevalonate-5PP Adenosine diphosphate Isopentenyl-PP Dimethylallylpyrophosphate Pyrophosphate Geranyl-PP Isopentenyl pyrophosphate Farnesyl pyrophosphate Pyrophosphate Hydrogen Ion NADPH Pyrophosphate NADP Squalene Cholesterol Adenosine triphosphate Adenosine diphosphate Phosphate Carbon dioxide Isopentenyl pyrophosphate Geranylgeranyl- PP Pyrophosphate Acetyl-CoA Water Acetoacetyl-CoA Coenzyme A Coenzyme A
FDPS FDPS HMGCLL1 MVK PMVK FDFT1 MVD GGPS1 HMGCS1 ACAT1 Alend Alend Alend Alend Alend HMG-CoA NADPH H+ NADP CoA Meval ATP Meva-5P ADP ATP Mev-5PP ADP Isop-PP Ipe PPi Gryl-PP IsopPyr FarPP PPi H+ NADPH PPi NADP Squalen Lanol ATP ADP Pi CO2 IsopPyr GGDP PPi Ac-CoA H2O ActaCoA CoA CoA Mg2+ Mg2+ Mg2+ Mg2+ Osteoclast Cytosol Alendronate enters the cell through endocytosis. The endocytic vesicles are acidified and the alendronate is released into the cytosol. Alendronate inhibit farnesyl pyrophosphate by binding in it's active site. Reduced production of farnesyl-PP, geranylgernayl-PP and other sterols which are essential for anchoring cell surface protein via prenylation, and are necessary for osteoclast function and survival. Low concentrations of these lipids prevents osteoclast attachment to the bone, thereby inducing apoptosis of the osteoclast, reducing osteoclast activity and bone resorption. Mevalonate Pathway Bone Loss Alendronate is administered orally and travels to the bone Alendronate acts to counteract osteoclast activity and reduce bone degradation
FDPS FDPS HMGCLL1 MVK PMVK FDFT1 MVD GGPS1 HMGCS1 ACAT1 Alend Alend Alend Alend Alend HMG-CoA NADPH H+ NADP CoA Meval ATP Meva-5P ADP ATP Mev-5PP ADP Isop-PP Ipe Ppi Gryl-PP IsopPyr FarPP Ppi H+ NADPH Ppi NADP Squalen Lanol ATP ADP Pi CO2 IsopPyr GGDP Ppi Ac-CoA H2O ActaCoA CoA CoA