Pathways

Alcloxa is a drug that is not metabolized by the human body as determined by current research and biotransformer analysis. Alcloxa passes through the liver and is then excreted from the body mainly through the kidney.

Aldosterone is a hormone produced in the zona glomerulosa of the adrenal cortex. It's function is to act on the distal convoluted tubule and the collecting duct of the nephron to make them more permeable to sodium to allow for its reuptake (in addition to allowing potassium wasting). As a result, water follows the sodium back into the body. The water retention contributes to an increased blood volume. Angiotensin II from the circulation binds to receptors on the zona glomerulosa cell membrane, activating the G protein and triggering a signaling cascade. The end result is the activation of the steroidogenic acute regulatory (StAR) protein that permits cholesterol uptake into the mitochondria. From there, cholesterol undergoes a series of reactions in both the mitochondrion and the smooth endoplasmic reticulum (steroidogenesis) where it finally becomes aldosterone.

Metabolites of Alectinib are predicted with biotransformer.

Alendronate (also known as alendronic acid) is a type of bisphosphonate medication with nitrogen that can inhibit FPP synthase, which can block the pathway that produce geranyl-PP and farnesyl pyrophosphate. Geranyl-PP and farnesyl pyrophosphate are the compounds that are required for small GTPase signalling proteins undergo post-translational farnesylation and geranylgeranylation. Therefore, lack the formation of geranyl-PP and farnesyl pyrophosphate can prevent osteoclast activity, which lead to prevention of reduced bone resorption and turnover.

Alendronate also known as alendronic acid is a bisphosphonate drug that is used to treat osteoporosis by preventing osteoclastic bone resorption. Alendronate is a second-generation bisphosphonate as it contains a nitrogen group that acts to inhibit farnesyl pyrophosphate synthase. It is administered orally, with low oral bioavailability it is recommended to not consume a meal an hour within the administration so as to not decrease the availability of the drug within the body. The drug binds to bone hydroxyapatite, when it undergoes resorption the alendronate is released and taken into the osteoclast by endocytosis. Within the cytosol of the osteoclast alendronate then acts by inhibiting farnesyl pyrophosphate synthase, which is essential for the prenylation of proteins needed for osteoclast survival. Some vitamin supplements may need to be taken in conjunction such as vitamin D , and avoidance of multivalent ions such as calcium, antacids and divalent ions as they will interrupt the absorption of the drug.

Alendronate is a second-generation bisphosphonate taken orally or IV and used for the treatment of conditions such as osteoporosis, Paget’s disease and hypercalcemia. Alendronate targets the mevalonate pathway in osteoclasts, the cells responsible for the break down of bone tissue. The mevalonate pathway starts off with acetyl-CoA forming acetoacetyl-CoA using acetyl-CoA acetyltransferase in the mitochondria. Acetyl-CoA and acetoacetyl-CoA then form HMG-CoA via HMG-CoA synthase. HMG-CoA is converted to mevalonate using the enzyme HMG-CoA reductase. Mevalonate kinase converts mevalonate into mevalonate-5P, which is then metabolized into mevalonate-5PP by phosphomevalonate kinase. Isopentenyl-PP is then formed from mevalonate-5PP via diphosphomevalonate decarboxylase. Farmesyl pyrophosphate converts isopentenyl-PP to geranyl-PP, then to farnesyl-PP. Farnesyl-PP goes on to form geranylgeranyl-PP through geranylgeranyl pyrophosphate synthase or squalene through squalene synthase. Squalene goes through a series of reactions to eventually form cholesterol. Alendronate binds to bone hydroxyapatite and when bone resorption occurs, alendronate enters the osteoclasts through endocytosis. Acidification of the endocytic vesicles releases the alendronate. Alendronate inhibits farnesyl pyrophosphate synthase, which reduces the production of downstream isoprenoid lipids like farnesyl-PP and geranylgeranyl-PP. these lipids are needed for a process called prenylation, to anchor cell surface proteins in the osteoclast membrane. Without prenylation, the osteoclast cannot attach to the bone, therefore they are unable to function and undergo apoptosis. This decreases bone resorption/ break down as the osteoclasts are no longer able to survive. Adverse effects like GI disturbances like peptic ulcers and oesophagitis, muscle and bone pain, stomach pain, osteonecrosis, diarrhea, constipation, nausea, flatulence, headache, dizziness and inflammatory responses may occur from taking alendronate.

Alendronic acid is a drug that is not metabolized by the human body as determined by current research and biotransformer analysis. Alendronic acid passes through the liver and is then excreted from the body mainly through the kidney.