Pathways

Bivalirudin is a direct thrombin inhibitor that treats heparin-induced thrombocytopenia and prevents thrombosis. It binds reversibly to the active site of thrombin inhibiting its activation of fibrinogen and coagulation factor XIII. Without the conversion of fibrinogen into fibrin the formation of a thrombus is stopped. Inactivation of coagulation factor XIII further inhibits blood clot formation, as this factor is responsible for stabilizing cross-linking fibrin creating the meshwork for the clot. This drug is commonly administered intravenously and is metabolized by proteolytic cleavage. Bivalirudin is cleared from plasma by the renal system and proteolytic cleavage. This drug interacts with food, echinacea needs to be avoided in addition to herbs and supplements that have anticoagulant and antiplatelet activity. These herbs and supplements include ginger, garlic, bilberry, danshen, piracetam and ginkgo biloba.

Bivalirudin is a synthetic peptide thrombin inhibitor that binds reversibly to the catalytic site and anion-binding exosite inhibiting the cleavage of fibrinogen into fibrin. Bivalirudin is used to treat heparin-induced thrombocytopenia as well as to prevent thrombosis. It is used in patients that are undergoing percutaneous coronary intervention or who have a risk in acute coronary syndromes caused by unstable angina or non-ST segment elevation. Thrombin is an important proteinase as it cleaves fibrinogen into fibrin monomers which help form the thrombus that forms the clot at the site of vascular injury. Because bivalirudin inhibits thrombin, clotting cannot form which is ideal for heart surgeries and some heart conditions. Bivalirudin should be monitored as it inhibits clotting so other injuries won't clot and it also can cause blood stagnation. Monitoring changes in hematocrit and blood pressure is extremely important when taking this drug. It is normally administered intravenously so that it is delivered to the site of action right away and can be controlled more easily.

Bivalirudin, trade name angiomax, is a direct thrombin inhibitor. It is often prescribed to patients who cannot take unfractionated or low molecular weight heparin. Bivalirudin does not need cofactor antithrobin to act. It binds circulating and clot-bound thrombin at the catalytic site and the anion binding exosite. The inhibition of fibrin prevents the cleavage of fibrinogen into fibrin which activates Factor XIII and Factor XIIIa. This destabilizes the thrombus and inhibits the promotion of thrombin production and platelet activation. As a result, bivalirudin prevents or reduces clot formation.

The Bloch pathway, named after Konrad Bloch, is the pathway following the mevalonate pathway occurring within the cell to complete cholesterol biosynthesis. Cholesterol is a necessary metabolite that helps create many essential hormones within the human body. This pathway, combined with the mevalonate pathway is one of two ways to biosynthesize cholesterol; the Kandutsch-Russell pathway is an alternative pathway that uses different compounds than the Bloch Pathway beginning after lanosterol. The first three reactions occur in the endoplasmic reticulum. Lanosterol, a compound created through the mevalonate pathway, binds with the enzyme lanosterol 14-alpha demethylase to become 4,4-dimethyl-14a-hydroxymethyl-5a-cholesta-8,24-dien-3b-ol. Moving to the next reaction, 4,4-dimethyl-14a-hydroxymethyl-5a-cholesta-8,24-dien-3b-ol utilizes the enzyme lanosterol 14-alpha demethylase to create 4,4-dimethyl-14α-formyl-5α-cholesta-8,24-dien-3β-ol. Lanosterol 14-alpha demethylase is used one last time in this pathway, converting 4,4-dimethyl-14α-formyl-5α-cholesta-8,24-dien-3β-ol into 4,4-dimethyl-5a-cholesta-8,14,24-trien-3b-ol. Entering the inner nuclear membrane, 4,4-dimethyl-5a-cholesta-8,14,24-trien-3b-ol is catalyzed by a lamin B receptor to create 4,4-dimethyl-5a-cholesta-8,24-dien-3-b-ol. Entering the endoplasmic reticulum membrane, 4,4-dimethyl-5a-cholesta-8,24-dien-3-b-ol, with the help of methyl monooxygenase 1 is converted to 4a-hydroxymethyl-4b-methyl-5a-cholesta-8,24-dien-3b-ol. The enzyme methyl monooxygenase 1 uses 4a-hydroxymethyl-4b-methyl-5a-cholesta-8,24-dien-3b-ol to produce 4a-formyl-4b-methyl-5a-cholesta-8,24-dien-3b-ol. This reaction is repeated once more, using 4a-formyl-4b-methyl-5a-cholesta-8,24-dien-3b-ol and methyl monooxygenase 1 to create 4a-carboxy-4b-methyl-5a-cholesta-8,24-dien-3b-ol. Briefly entering the endoplasmic reticulum, 4a-carboxy-4b-methyl-5a-cholesta-8,24-dien-3b-ol then uses sterol-4-alpha-carboxylate-3-dehyrogenase to catalyze into 3-keto-4-methylzymosterol. Back in the endoplasmic reticulum membrane, where the pathway will continue on for the remaining reactions, 3-keto-4-methylzymosterol combines with 3-keto-steroid reductase to create 4a-methylzymosterol. 4a-Methylzymosterol joins the enzyme methylsterol monooxgenase 1 to result in 4a-hydroxymethyl-5a-cholesta-8,24-dien-3b-ol. 4a-Hydroxymethyl-5a-cholesta-8,24-dien-3b-ol uses methylsterol monooxygenase 1 to convert to 4a-formyl-5a-cholesta-8,24-dien-3b-ol. 4a-Formyl-5a-cholesta-8,24-dien-3b-ol proceeds to use the same enzyme used in the previous reaction: methylsterol monooxygenase 1, to catalyze into 4a-carboxy-5a-cholesta-8,24-dien-3b-ol. Sterol-4-alpha-carboxylate-3-dehydrogenase is used alongside 4a-carboxy-5a-cholesta-8,24-dien-3b-ol to produce 5a-cholesta-8,24-dien-3-one (also known as zymosterone). Zymosterone (5a-cholesta-8,24-dien-3-one) teams up with 3-keto-steroid reductase to create zymosterol. Zymosterol proceeds to use the enzyme 3-beta-hydroxysteroid-delta(8),delta(7)-isomerase to catalyze into 5a-cholesta-7,24-dien-3b-ol. The compound 5a-cholesta-7,24-dien-3b-ol then joins lathosterol oxidase to convert to 7-dehydrodesmosterol. 7-Dehydrodesmosterol and the enzyme 7-dehydrocholesterol reductase come together to create desmosterol. This brings the pathway to the final reaction, where desmosterol combines with delta(24)-sterol reductase to finally convert to cholesterol.

Blue diaper syndrome is a recessive metabolic disorder that has not yet been determined to be X-linked or autosomal. This syndrome is caused by a mutation in the large neutral amino acids transporter small subunit 1 protein, which allows tryptophan, among other amino acids, to be reabsorbed in the kidneys. The excess tryptophan found in the intestine is digested by bacteria which excrete indole, which can undergo oxidation to produce indigo blue. This is seen in the diapers of infants affected by blue diaper syndrome, due to the increased levels of indole in their urine or feces. Other symptoms can include bacterial infections, damage to various parts of the eye, hypercalcemia, and impaired kidney function due to this. Treatment can include a calcium restricted diet in order to prevent hypercalcemia, and a tryptophan restricted diet to prevent all systems. If bacterial infections are common, antibiotics may be prescribed.

Blue diaper syndrome is a recessive metabolic disorder that has not yet been determined to be X-linked or autosomal. This syndrome is caused by a mutation in the large neutral amino acids transporter small subunit 1 protein, which allows tryptophan, among other amino acids, to be reabsorbed in the kidneys. The excess tryptophan found in the intestine is digested by bacteria which excrete indole, which can undergo oxidation to produce indigo blue. This is seen in the diapers of infants affected by blue diaper syndrome, due to the increased levels of indole in their urine or feces. Other symptoms can include bacterial infections, damage to various parts of the eye, hypercalcemia, and impaired kidney function due to this. Treatment can include a calcium restricted diet in order to prevent hypercalcemia, and a tryptophan restricted diet to prevent all systems. If bacterial infections are common, antibiotics may be prescribed.

Blue diaper syndrome is a recessive metabolic disorder that has not yet been determined to be X-linked or autosomal. This syndrome is caused by a mutation in the large neutral amino acids transporter small subunit 1 protein, which allows tryptophan, among other amino acids, to be reabsorbed in the kidneys. The excess tryptophan found in the intestine is digested by bacteria which excrete indole, which can undergo oxidation to produce indigo blue. This is seen in the diapers of infants affected by blue diaper syndrome, due to the increased levels of indole in their urine or feces. Other symptoms can include bacterial infections, damage to various parts of the eye, hypercalcemia, and impaired kidney function due to this. Treatment can include a calcium restricted diet in order to prevent hypercalcemia, and a tryptophan restricted diet to prevent all systems. If bacterial infections are common, antibiotics may be prescribed.

Boceprevir is a hepatitis C virus NS3/4A protease inhibitor used in combination with other medications to treat chronic hepatitis C genotype 1 infection. Hepatitis C virus lipoviroparticles enter target hepatocytes via receptor-mediated endocytosis. The lipoviroparticles attach to LDL-R and SR-B1, and then the virus binds to CD81 and subsequently claudin-1 and occludin, which mediate the late steps of viral entry. The virus is internalized by clathrin-dependent endocytosis. RNA is released from the mature Hepatitis C virion and translated at the rough endoplasmic reticulum into a single Genome polyprotein. Boceprevir accumulates in the liver after uptake into hepatocytes via solute carrier organic anion transporter family member 1B1. Boceprevir inhibits NS3/4A protease, which is an enzyme that cleaves the heptatitis C virus polyprotein downstream of the NS3 proteolytic site, which generates nonstructural proteins NS3, NS4A, NS4B, NS5A, and NS5B. These proteins are required in viral RNA replication, therefore because of the inhibition of their formation, RNA replication cannot occur. Because RNA replication does not occur, the mature virion is unable to form.