Pathways

Wilson disaease

Warfarin is an anticoagulant drug normally used to prevent blood clot formation as well as migration. Indicated for: prophylaxis and treatment of venous thromboembolism and related pulmonary embolism, prophylaxis and treatment of thromboembolism associated with atrial fibrillation, prophylaxis and treatment of thromboembolism associated with cardiac valve replacement, use as adjunct therapy to reduce mortality, recurrent myocardial infarction, and thromboembolic events post myocardial infarction. Off-label uses include secondary prevention of stroke and transient ischemic attacks in patients with rheumatic mitral valve disease but without atrial fibrillation. Warfarin does not actually affect blood viscosity, rather, it inhibits vitamin-k dependent synthesis of biologically active forms of various clotting factors in addition to several regulatory factors. Warfarin is a [vitamin K] antagonist which acts to inhibit the production of vitamin K by inhibiting vitamin K epoxide reductase. By doing this the carboxylation of vitamin-k dependent factors such as II, VII, IX and X are prevented. As the concentration of reduced form of vitamin K decreases this leads to a depletion of the cofactor for future reactions that are vitamin k dependent. This ultimately leads to interference with coagulation, because of this patient should not give blood during the time they are using Warfarin. Warfarin has several properties that should be noted when used medicinally, including its ability to cross the placental barrier during pregnancy which can result in fetal bleeding, spontaneous abortion, preterm birth, stillbirth, and neonatal death. Additional adverse effects such as necrosis, purple toe syndrome, osteoporosis, valve and artery calcification, and drug interactions have also been documented with warfarin use.

Warfarin is a drug part of the anticoagulant drug class, used to dissolve or break down blood clots. Warfarin inhibits vitamin K epoxide reductase complex subunit 1. In the endoplasmic reticulum within the liver, vitamin K1 2,3-epoxide would regularly use vitamin K epoxide reductase complex subunit 1 to become reduced vitamin K (phylloquinone), and then back to vitamin K1 2,3-epoxide continually through vitamin K-dependent gamma-carboxylase, but as warfarin inhibits vitamin K epoxide reductase complex subunit 1, this causes a decreased amount of the reduced form of vitamin K, which in turn causes a decreased coagulability of the blood. The enzyme vitamin K-dependent gamma carboxylase catalyzes precursors of prothrombin and coagulation factors VII, IX and X to prothrombin, and coagulation factors VII, IX and X. From there, these precursors and factors leave the liver cell and enter into the blood capillary bed. Once there, prothrombin is catalyzed into the protein complex prothrombinase complex which is made up of coagulation factor Xa/coagulation factor Va (platelet factor 3). These factors are joined by coagulation factor V. Through the two factors coagulation factor Xa and coagulation factor Va, thrombin is produced, which then uses fibrinogen alpha, beta, and gamma chains to create fibrin (loose). This is then turned into coagulation factor XIIIa, which is activated through coagulation factor XIII A and B chains. From here, fibrin (mesh) is produced which interacts with endothelial cells to cause coagulation. Plasmin is then created from fibrin (mesh), then joined by tissue-type plasminogen activator (reteplase) through plasminogen, and creates fibrin degradation products. These are enzymes that stay in your blood after your body has dissolved a blood clot. Coming back to the factors transported from the liver, coagulation factor X is catalyzed into a group of enzymes called the tenase complex: coagulation factor IX and coagulation factor VIIIa (platelet factor 3). This protein complex is also contributed to by coagulation factor VIII, which through prothrombin is catalyzed into coagulation factor VIIIa. From there, this protein complex is catalyzed into prothrombinase complex, the group of proteins mentioned above, contributing to the above process ending in fibrin degradation products. Another enzyme transported from the liver is coagulation factor IX which becomes coagulation factor IXa, part of the tense complex, through coagulation factor XIa. Coagulation factor XIa is produced through coagulation factor XIIa which converts coagulation XI to become coagulation factor XIa. Coagulation factor XIIa is introduced through chain of activation starting in the endothelial cell with collagen alpha-1 (I) chain, which paired with coagulation factor XII activates coagulation factor XIIa. It is also activated through plasma prekallikrein and coagulation factor XIIa which activate plasma kallikrein, which then pairs with coagulation factor XII simultaneously with the previous collagen chain pairing to activate coagulation XIIa. Lastly, the previously transported coagulation factor VII and tissue factor coming from a vascular injury work together to activate tissue factor: coagulation factor VIIa. This enzyme helps coagulation factor X catalyze into coagulation factor Xa, to contribute to the prothrombinase complex and complete the pathway.

Warfarin is an anticoagulant that inhibits the liver enzyme vitamin K reductase. This leads to the depletion of the reduced form of vitamin K (vitamin KH2). As vitamin K is a cofactor for the gamma-carboxylation and subsequent activation of the vitamin K-dependent coagulation factors (II, VII, IX, and X), this ultimately results in reduced cleavage of fibrinogen into fibrin and decreased coagulability of the blood.

The Warburg Effect refers to the phenomenon that occurs in most cancer cells where instead of generating energy with a low rate of glycolysis followed by oxidizing pyruvate via the Krebs cycle in the mitochondria, the pyruvate from a high rate of glycolysis undergoes lactic acid fermentation in the cytosol. As the Krebs cycle is an aerobic process, in normal cells lactate production is reserved for anaerobic conditions. However, cancer cells preferentially utilize glucose for lactate production via this “aerobic glycolysis”, even when oxygen is plentiful. The Warburg Effect is thought to be the result of mutations to oncogenes and tumour suppressor genes. It may be an adaptation to low-oxygen environments within tumors, the result of cancer genes shutting down the mitochondria, or a mechanism to aid cell proliferation via increased glycolysis. The Warburg Effect involves numerous pathways, including growth factor stimulation, transcriptional activation, and glycolysis promotion. A notable alteration in prostate cancer cell is the decreased levels of zincs in the cell which allow for the use of citrate in the TCA cycle. High levels of Sarcosine have also been detected in hormone-dependent prostate cancer.