Pathways

Metabolites of Retapamulin are predicted with biotransformer.

Reteplase 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 myocardial infarction, cardiovascular mortality and congestive heart failure. 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.

Reteplase is an enzyme that is part of the thrombolytics drug class, used to dissolve or break down blood clots. Reteplase activates plasminogen. Then zooming in even further to the endoplasmic reticulum within the liver, vitamin K1 2,3-epoxide uses 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. This enzyme also 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.

Reteplase is a plasminogen activator that is created as a purified form of human tissue, also known as Retavase that is used in emergencies such as myocardial infarction, ischemic stroke and pulmonary emboli. Reteplase is administered intravenously and travels through the bloodstream and acts on plasminogen cleaving an arginine-valine bond converting it to its active form plasmin. Plasmin then goes to act on the fibrin matrix and degrades it into its products eliminating the blood clot.

Retinol is part of the vitamin A family, and is known as vitamin A1, and in a dietary context it is a type of preformed vitamin A. As with other preformed vitamin A's, it can be obtained from animal sources, with the highest concentrations coming from animal liver, with other sources being fish and dairy products. Other forms of vitamin A include retinal, its aldehyde form, retinoic acid, its acid form, and reinyl ester, its ester form. Additionally, herbivores and omnivores can obtain provitamin A from things such as alpha-, beta- and gamma-carotene, which can be converted to retinol as needed by the body. Retinol can be used in the body to form retinyl ester via diacylglycerol O-acyltransferase 1 and acyl-CoA wax akcohol acyltransferase 1 which both use acetyl-CoA as a reactant and produce CoA in addition to the retinyl ester. IT can also be produced by lecithin retinol acyltransferase, which uses a phosphatidylcholine molecule, and produces glycerophosphocholine. All of these reactions take place in the endoplasmic reticulum. Retinyl ester can also be converted back to retinol by patatin-like phospholipase domain-containing protein 4 as the enzyme in a reaction that also converts a diacylglycerol to a triacylglycerol. Alternately, retinyl ester can interact with retinoid isomerohydrolase to form 11-cis-retinol. 11-cis-retinol can be converted to retinyl palmitate by either diacylglycerol O-acyltransferase 1 or acyl-CoA wax alcohol acyltransferase 1 in the endoplasmic reticulum, which both add the acetyl group onto 11-cis-retinol, forming CoA as a side product. Alternatively, retinyl palmitate can be formed by lecithin retinol acyltransferase, which takes a molecule of phosphatidylcholine, and produces glycerophosphocholine in addition to the retinyl palmitate. Rhodopsin, a photosensitive protein found in the retina, can be converted to bathorhodopsin, which has previously been known as prelumirhodopsin. This conversion is caused by the absorption of light into the retinal portion of the protein complex, which then isomerizes, forcing the protein to change shape to accomodate this. Bathorhodopsin almost immediately converts to lumirhodopsin, which then converts to metarhodopsin, and at this point, the retinal is in its all-trans configuration. All-trans retinal can also be formed from 11-cis-retinaldehyde, also known as 11-cis-retinal, via dehydrogenase/reductase SDR family member 4 or retinol dehydrogenase 12 in the cell, as well as retinol dehydrogenases 8 and 16, short-chain dehydrogenase/reductase 3 or dehydrogenase/reductase SRD family member 9 in the endoplasmic reticulum. Two molecules of retinal can also be formed from beta-carotene, after its interaction with betabeta-carotene 15,15'-monooxygenase, or from retinol via retinol dehydrogenase 11 in the endoplasmic reticulum. Additionally, 11-cis-retinaldehyde can reversibly form all-trans retinal via interaction with alcohol dehydrogenase 1A. 11-cis-retinaldehyde is also in the conformation found in rhodopsin, and can be used to create more rhodopsin complexes. 11-cis-retinaldehyde can also be converted to 11-cis-retinol by retinol dehydrogenase in the endoplasmic reticulum. Retinol can also isomerize and form 9-cis-retinol, which can then be reversibly oxidized to form 9-cis-retinal by interacting with either retinol dehydrogenase 11 or dehydrogenase/reductase SDR family member 4. 9-cis-retinal can then be further oxidized to 9-cis-retinoic acid by retinal dehydrogenase 1 or 2. 9-cis-retinoic acid can also be formed from the isomerization of all-trans retinoic acid, which in turn is formed by the oxidation of retinol by either of retinal dehydrogenase 1 or 2. All-trans retinoic acid can also be glucuronidated to form retinoyl b-glucuronide, in a reaction catalyzed by a multiprotein chaperone complex including UDP-glucuronosyltransferase 1-1 in the endoplasmic reticulum. Finally, in the endoplasmic reticulum, all-trans-retinoic acid can undergo epoxidation to form all-trans-5,6-epoxyretinoic acid by interaction with a complex of cytochrome P450 proteins, or hydroxylated to either 4-hydroxyretinoic acid or all-trans-18-hydroxyretinoic acid by cytochrome P450 26A1. In one last reqction, 4-hydroxyretinoic acid can be oxidized once again by cytochrome P450 26A1 to form 4-oxo-retinoic acid.

Retinol is part of the vitamin A family, and is known as vitamin A1, and in a dietary context it is a type of preformed vitamin A. As with other preformed vitamin A's, it can be obtained from animal sources, with the highest concentrations coming from animal liver, with other sources being fish and dairy products. Other forms of vitamin A include retinal, its aldehyde form, retinoic acid, its acid form, and reinyl ester, its ester form. Additionally, herbivores and omnivores can obtain provitamin A from things such as alpha-, beta- and gamma-carotene, which can be converted to retinol as needed by the body. Retinol can be used in the body to form retinyl ester via diacylglycerol O-acyltransferase 1 and acyl-CoA wax akcohol acyltransferase 1 which both use acetyl-CoA as a reactant and produce CoA in addition to the retinyl ester. IT can also be produced by lecithin retinol acyltransferase, which uses a phosphatidylcholine molecule, and produces glycerophosphocholine. All of these reactions take place in the endoplasmic reticulum. Retinyl ester can also be converted back to retinol by patatin-like phospholipase domain-containing protein 4 as the enzyme in a reaction that also converts a diacylglycerol to a triacylglycerol. Alternately, retinyl ester can interact with retinoid isomerohydrolase to form 11-cis-retinol. 11-cis-retinol can be converted to retinyl palmitate by either diacylglycerol O-acyltransferase 1 or acyl-CoA wax alcohol acyltransferase 1 in the endoplasmic reticulum, which both add the acetyl group onto 11-cis-retinol, forming CoA as a side product. Alternatively, retinyl palmitate can be formed by lecithin retinol acyltransferase, which takes a molecule of phosphatidylcholine, and produces glycerophosphocholine in addition to the retinyl palmitate. Rhodopsin, a photosensitive protein found in the retina, can be converted to bathorhodopsin, which has previously been known as prelumirhodopsin. This conversion is caused by the absorption of light into the retinal portion of the protein complex, which then isomerizes, forcing the protein to change shape to accomodate this. Bathorhodopsin almost immediately converts to lumirhodopsin, which then converts to metarhodopsin, and at this point, the retinal is in its all-trans configuration. All-trans retinal can also be formed from 11-cis-retinaldehyde, also known as 11-cis-retinal, via dehydrogenase/reductase SDR family member 4 or retinol dehydrogenase 12 in the cell, as well as retinol dehydrogenases 8 and 16, short-chain dehydrogenase/reductase 3 or dehydrogenase/reductase SRD family member 9 in the endoplasmic reticulum. Two molecules of retinal can also be formed from beta-carotene, after its interaction with betabeta-carotene 15,15'-monooxygenase, or from retinol via retinol dehydrogenase 11 in the endoplasmic reticulum. Additionally, 11-cis-retinaldehyde can reversibly form all-trans retinal via interaction with alcohol dehydrogenase 1A. 11-cis-retinaldehyde is also in the conformation found in rhodopsin, and can be used to create more rhodopsin complexes. 11-cis-retinaldehyde can also be converted to 11-cis-retinol by retinol dehydrogenase in the endoplasmic reticulum. Retinol can also isomerize and form 9-cis-retinol, which can then be reversibly oxidized to form 9-cis-retinal by interacting with either retinol dehydrogenase 11 or dehydrogenase/reductase SDR family member 4. 9-cis-retinal can then be further oxidized to 9-cis-retinoic acid by retinal dehydrogenase 1 or 2. 9-cis-retinoic acid can also be formed from the isomerization of all-trans retinoic acid, which in turn is formed by the oxidation of retinol by either of retinal dehydrogenase 1 or 2. All-trans retinoic acid can also be glucuronidated to form retinoyl b-glucuronide, in a reaction catalyzed by a multiprotein chaperone complex including UDP-glucuronosyltransferase 1-1 in the endoplasmic reticulum. Finally, in the endoplasmic reticulum, all-trans-retinoic acid can undergo epoxidation to form all-trans-5,6-epoxyretinoic acid by interaction with a complex of cytochrome P450 proteins, or hydroxylated to either 4-hydroxyretinoic acid or all-trans-18-hydroxyretinoic acid by cytochrome P450 26A1. In one last reqction, 4-hydroxyretinoic acid can be oxidized once again by cytochrome P450 26A1 to form 4-oxo-retinoic acid.

Retinol is part of the vitamin A family, and is known as vitamin A1, and in a dietary context it is a type of preformed vitamin A. As with other preformed vitamin A's, it can be obtained from animal sources, with the highest concentrations coming from animal liver, with other sources being fish and dairy products. Other forms of vitamin A include retinal, its aldehyde form, retinoic acid, its acid form, and reinyl ester, its ester form. Additionally, herbivores and omnivores can obtain provitamin A from things such as alpha-, beta- and gamma-carotene, which can be converted to retinol as needed by the body. Retinol can be used in the body to form retinyl ester via diacylglycerol O-acyltransferase 1 and acyl-CoA wax akcohol acyltransferase 1 which both use acetyl-CoA as a reactant and produce CoA in addition to the retinyl ester. IT can also be produced by lecithin retinol acyltransferase, which uses a phosphatidylcholine molecule, and produces glycerophosphocholine. All of these reactions take place in the endoplasmic reticulum. Retinyl ester can also be converted back to retinol by patatin-like phospholipase domain-containing protein 4 as the enzyme in a reaction that also converts a diacylglycerol to a triacylglycerol. Alternately, retinyl ester can interact with retinoid isomerohydrolase to form 11-cis-retinol. 11-cis-retinol can be converted to retinyl palmitate by either diacylglycerol O-acyltransferase 1 or acyl-CoA wax alcohol acyltransferase 1 in the endoplasmic reticulum, which both add the acetyl group onto 11-cis-retinol, forming CoA as a side product. Alternatively, retinyl palmitate can be formed by lecithin retinol acyltransferase, which takes a molecule of phosphatidylcholine, and produces glycerophosphocholine in addition to the retinyl palmitate. Rhodopsin, a photosensitive protein found in the retina, can be converted to bathorhodopsin, which has previously been known as prelumirhodopsin. This conversion is caused by the absorption of light into the retinal portion of the protein complex, which then isomerizes, forcing the protein to change shape to accomodate this. Bathorhodopsin almost immediately converts to lumirhodopsin, which then converts to metarhodopsin, and at this point, the retinal is in its all-trans configuration. All-trans retinal can also be formed from 11-cis-retinaldehyde, also known as 11-cis-retinal, via dehydrogenase/reductase SDR family member 4 or retinol dehydrogenase 12 in the cell, as well as retinol dehydrogenases 8 and 16, short-chain dehydrogenase/reductase 3 or dehydrogenase/reductase SRD family member 9 in the endoplasmic reticulum. Two molecules of retinal can also be formed from beta-carotene, after its interaction with betabeta-carotene 15,15'-monooxygenase, or from retinol via retinol dehydrogenase 11 in the endoplasmic reticulum. Additionally, 11-cis-retinaldehyde can reversibly form all-trans retinal via interaction with alcohol dehydrogenase 1A. 11-cis-retinaldehyde is also in the conformation found in rhodopsin, and can be used to create more rhodopsin complexes. 11-cis-retinaldehyde can also be converted to 11-cis-retinol by retinol dehydrogenase in the endoplasmic reticulum. Retinol can also isomerize and form 9-cis-retinol, which can then be reversibly oxidized to form 9-cis-retinal by interacting with either retinol dehydrogenase 11 or dehydrogenase/reductase SDR family member 4. 9-cis-retinal can then be further oxidized to 9-cis-retinoic acid by retinal dehydrogenase 1 or 2. 9-cis-retinoic acid can also be formed from the isomerization of all-trans retinoic acid, which in turn is formed by the oxidation of retinol by either of retinal dehydrogenase 1 or 2. All-trans retinoic acid can also be glucuronidated to form retinoyl b-glucuronide, in a reaction catalyzed by a multiprotein chaperone complex including UDP-glucuronosyltransferase 1-1 in the endoplasmic reticulum. Finally, in the endoplasmic reticulum, all-trans-retinoic acid can undergo epoxidation to form all-trans-5,6-epoxyretinoic acid by interaction with a complex of cytochrome P450 proteins, or hydroxylated to either 4-hydroxyretinoic acid or all-trans-18-hydroxyretinoic acid by cytochrome P450 26A1. In one last reqction, 4-hydroxyretinoic acid can be oxidized once again by cytochrome P450 26A1 to form 4-oxo-retinoic acid.

Retinol is part of the vitamin A family, and is known as vitamin A1, and in a dietary context it is a type of preformed vitamin A. As with other preformed vitamin A's, it can be obtained from animal sources, with the highest concentrations coming from animal liver, with other sources being fish and dairy products. Other forms of vitamin A include retinal, its aldehyde form, retinoic acid, its acid form, and reinyl ester, its ester form. Additionally, herbivores and omnivores can obtain provitamin A from things such as alpha-, beta- and gamma-carotene, which can be converted to retinol as needed by the body. Retinol can be used in the body to form retinyl ester via diacylglycerol O-acyltransferase 1 and acyl-CoA wax akcohol acyltransferase 1 which both use acetyl-CoA as a reactant and produce CoA in addition to the retinyl ester. IT can also be produced by lecithin retinol acyltransferase, which uses a phosphatidylcholine molecule, and produces glycerophosphocholine. All of these reactions take place in the endoplasmic reticulum. Retinyl ester can also be converted back to retinol by patatin-like phospholipase domain-containing protein 4 as the enzyme in a reaction that also converts a diacylglycerol to a triacylglycerol. Alternately, retinyl ester can interact with retinoid isomerohydrolase to form 11-cis-retinol. 11-cis-retinol can be converted to retinyl palmitate by either diacylglycerol O-acyltransferase 1 or acyl-CoA wax alcohol acyltransferase 1 in the endoplasmic reticulum, which both add the acetyl group onto 11-cis-retinol, forming CoA as a side product. Alternatively, retinyl palmitate can be formed by lecithin retinol acyltransferase, which takes a molecule of phosphatidylcholine, and produces glycerophosphocholine in addition to the retinyl palmitate. Rhodopsin, a photosensitive protein found in the retina, can be converted to bathorhodopsin, which has previously been known as prelumirhodopsin. This conversion is caused by the absorption of light into the retinal portion of the protein complex, which then isomerizes, forcing the protein to change shape to accomodate this. Bathorhodopsin almost immediately converts to lumirhodopsin, which then converts to metarhodopsin, and at this point, the retinal is in its all-trans configuration. All-trans retinal can also be formed from 11-cis-retinaldehyde, also known as 11-cis-retinal, via dehydrogenase/reductase SDR family member 4 or retinol dehydrogenase 12 in the cell, as well as retinol dehydrogenases 8 and 16, short-chain dehydrogenase/reductase 3 or dehydrogenase/reductase SRD family member 9 in the endoplasmic reticulum. Two molecules of retinal can also be formed from beta-carotene, after its interaction with betabeta-carotene 15,15'-monooxygenase, or from retinol via retinol dehydrogenase 11 in the endoplasmic reticulum. Additionally, 11-cis-retinaldehyde can reversibly form all-trans retinal via interaction with alcohol dehydrogenase 1A. 11-cis-retinaldehyde is also in the conformation found in rhodopsin, and can be used to create more rhodopsin complexes. 11-cis-retinaldehyde can also be converted to 11-cis-retinol by retinol dehydrogenase in the endoplasmic reticulum. Retinol can also isomerize and form 9-cis-retinol, which can then be reversibly oxidized to form 9-cis-retinal by interacting with either retinol dehydrogenase 11 or dehydrogenase/reductase SDR family member 4. 9-cis-retinal can then be further oxidized to 9-cis-retinoic acid by retinal dehydrogenase 1 or 2. 9-cis-retinoic acid can also be formed from the isomerization of all-trans retinoic acid, which in turn is formed by the oxidation of retinol by either of retinal dehydrogenase 1 or 2. All-trans retinoic acid can also be glucuronidated to form retinoyl b-glucuronide, in a reaction catalyzed by a multiprotein chaperone complex including UDP-glucuronosyltransferase 1-1 in the endoplasmic reticulum. Finally, in the endoplasmic reticulum, all-trans-retinoic acid can undergo epoxidation to form all-trans-5,6-epoxyretinoic acid by interaction with a complex of cytochrome P450 proteins, or hydroxylated to either 4-hydroxyretinoic acid or all-trans-18-hydroxyretinoic acid by cytochrome P450 26A1. In one last reqction, 4-hydroxyretinoic acid can be oxidized once again by cytochrome P450 26A1 to form 4-oxo-retinoic acid.