Pathways

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

Altretamine, also known as Hexalen, is a novel alkylating agent from the antineoplastic drug class. This drug is used as a palliative treatment for patients with persistent or recurrent ovarian cancer. The precise mechanism of action of the drug is still not completely understood. It is known that following administration, the molecule goes through N-demethylation by the cytochrome P450 monooxygenases in the liver. This generates carbinalamine as an intermediate leading after to the formaldehyde and smaller inactive compounds. When the carbinalamine losses its hydroxy group, it gives the iminium species. This last molecule is the one that probably binds to DNA. This drug is administered as an oral capsule.

The alternative complement pathway is one of the three complement pathways, the other two being classical and lectin. These pathways work innately to opsonize pathogens and kill them. The alternative pathway is activated with the complement C3 protein is cleaved spontaneously in the blood. The C3b component is then free to covalently bond to the surface of pathogens or apoptotic cells, acting as a tag for other parts of the immune system. Complement factor B is cleaved into factors Ba and Bb, and factor Bb can then bind to complement factor C3b on the surface of the pathogen along with a water molecule. This complex is known as fluid-phase C3 convertase, and it cleaves many more C3 proteins into C3a and C3b. Properdin is another compound that is important for complement activation, and it binds to the C3bBb complex, stabilizing it and forming the C3bBbP complex. This complex then can bind another C3b protein, and it then functions as a C5 convertase, splitting C5 into C5a and C5b. At this point, the remainder of the pathway is the same between the alternative and classical pathways. The complement C5b protein binds to and forms a complex with component C6, followed by C7, C8 and C9. Multiple molecules of C9 end up binding to this complex, and this is what forms the membrane attack complex pore that allows for uncontrolled diffusion of the cell’s contents, and if enough pores are formed, the cell will be killed.

The alternative complement pathway is one of the three complement pathways, the other two being classical and lectin. These pathways work innately to opsonize pathogens and kill them. The alternative pathway is activated with the complement C3 protein is cleaved spontaneously in the blood. The C3b component is then free to covalently bond to the surface of pathogens or apoptotic cells, acting as a tag for other parts of the immune system. Complement factor B is cleaved into factors Ba and Bb, and factor Bb can then bind to complement factor C3b on the surface of the pathogen along with a water molecule. This complex is known as fluid-phase C3 convertase, and it cleaves many more C3 proteins into C3a and C3b. Properdin is another compound that is important for complement activation, and it binds to the C3bBb complex, stabilizing it and forming the C3bBbP complex. This complex then can bind another C3b protein, and it then functions as a C5 convertase, splitting C5 into C5a and C5b. At this point, the remainder of the pathway is the same between the alternative and classical pathways. The complement C5b protein binds to and forms a complex with component C6, followed by C7, C8 and C9. Multiple molecules of C9 end up binding to this complex, and this is what forms the membrane attack complex pore that allows for uncontrolled diffusion of the cell’s contents, and if enough pores are formed, the cell will be killed.

The alternative complement pathway is one of the three complement pathways, the other two being classical and lectin. These pathways work innately to opsonize pathogens and kill them. The alternative pathway is activated with the complement C3 protein is cleaved spontaneously in the blood. The C3b component is then free to covalently bond to the surface of pathogens or apoptotic cells, acting as a tag for other parts of the immune system. Complement factor B is cleaved into factors Ba and Bb, and factor Bb can then bind to complement factor C3b on the surface of the pathogen along with a water molecule. This complex is known as fluid-phase C3 convertase, and it cleaves many more C3 proteins into C3a and C3b. Properdin is another compound that is important for complement activation, and it binds to the C3bBb complex, stabilizing it and forming the C3bBbP complex. This complex then can bind another C3b protein, and it then functions as a C5 convertase, splitting C5 into C5a and C5b. At this point, the remainder of the pathway is the same between the alternative and classical pathways. The complement C5b protein binds to and forms a complex with component C6, followed by C7, C8 and C9. Multiple molecules of C9 end up binding to this complex, and this is what forms the membrane attack complex pore that allows for uncontrolled diffusion of the cell’s contents, and if enough pores are formed, the cell will be killed.

The alternative complement pathway is one of the three complement pathways, the other two being classical and lectin. These pathways work innately to opsonize pathogens and kill them. The alternative pathway is activated with the complement C3 protein is cleaved spontaneously in the blood. The C3b component is then free to covalently bond to the surface of pathogens or apoptotic cells, acting as a tag for other parts of the immune system. Complement factor B is cleaved into factors Ba and Bb, and factor Bb can then bind to complement factor C3b on the surface of the pathogen along with a water molecule. This complex is known as fluid-phase C3 convertase, and it cleaves many more C3 proteins into C3a and C3b. Properdin is another compound that is important for complement activation, and it binds to the C3bBb complex, stabilizing it and forming the C3bBbP complex. This complex then can bind another C3b protein, and it then functions as a C5 convertase, splitting C5 into C5a and C5b. At this point, the remainder of the pathway is the same between the alternative and classical pathways. The complement C5b protein binds to and forms a complex with component C6, followed by C7, C8 and C9. Multiple molecules of C9 end up binding to this complex, and this is what forms the membrane attack complex pore that allows for uncontrolled diffusion of the cell’s contents, and if enough pores are formed, the cell will be killed.

Alteplase is fibrinolytic drug that functions as a recombinant tissue plasminogen activator. It is administered intravenously and used to treat conditions caused by arterial blood clots such as acute ischemic stroke, acute myocardial infarction, acute massive pulmonary embolism and blocked central venous access devices. It targets plasminogen in blood vessels where these clots occur. The clotting process consists of two pathways, intrinsic and extrinsic, which converge to create stable fibrin which traps platelets and forms a hemostatic plug. The intrinsic pathway is activated by trauma inside the vasculature system, when there is exposed endothelial collagen. Endothelial collagen only becomes exposed when there is damage. The pathway starts with plasma kallikrein activating factor XII. The activated factor XIIa activates factor XI. Factor IX is then activated by factor XIa. Thrombin activates factor VIII and a Calicum-phospholipid-XIIa-VIIIa complex forms. This complex then activates factor X, the merging point of the two pathways. The extrinsic pathway is activated when external trauma causes blood to escape the vasculature system. Activation occurs through tissue factor released by endothelial cells after external damage. The tissue factor is a cellular receptor for factor VII. In the presence of calcium, the active site transitions and a TF-VIIa complex is formed. This complex aids in activation of factors IX and X. Factor V is activated by thrombin in the presence of calcium, then the activated factor Xa, in the presence of phospholipid, calcium and factor Va can convert prothrombin to thrombin. The extrinsic pathway occurs first, producing a small amount of thrombin, which then acts as a positive feedback on several components to increase the thrombin production. Thrombin converts fibrinogen to a loose, unstable fibrin and also activates factor XIII. Factors XIIIa strengthens the fibrin-fibrin and forms a stable, mesh fibrin which is essential for clot formation. The blood clot can be broken down by the enzyme plasmin. Plasmin is formed from plasminogen by tissue plasminogen activator. Alteplase acts as a tissue plasminogen activator. It binds to clots with fibrin where it causes hydrolysis of the arginine-valine bond in plasminogen, aiding its conversion to plasmin. The plasmin degrades the stable fibrin and causes lysis of the clot. The activity of alteplase depends on the presence of fibrin. Only small amounts of plasmin is formed from plasminogen when there is no fibrin. Alteplase in the presence of fibrin obtains a higher affinity for plasminogen, thus leading to its increased activity. Alteplase undergoes hepatic metabolism and is excreted in urine. Adverse effects such as bleeding, nausea, vomiting, anaphylaxis, fever and angioedema can occur from the use of alteplase.