Pathways

Steroidogenesis is a process that through the transformations of other steroids, produces a desired steroid. Some of these desired steroids include cortisol, corticoids, testosterone, estrogens, aldosterone and progesterone. To begin the synthesis of steroid hormones, cholesterol synthesizes a hormone called pregnenolone. This is done by cholesterol from the cytosol or lysosome being brought to the mitochondria and becoming fixed in the inner mitochondrial membrane. Once there, the cholesterol becomes pregnenolone through three reactions. The enzyme responsible for catalyzing all three reactions is CYP11A, a side chain cleavage enzyme. After being created, the pregnenolone enters the cytosol, where the cholesterol originated. Once in the cytosol, pregenolone synthesizes progesterone, using two reactions. These two reactions are both catalyzed by an enzyme called 3-beta-hydroxysteroid dehydrogenase/isomerase. The enzyme CYP21A2 then hydroxylates progesterone, which converts it to deoxycorticosterone. Deoxycorticosterone then undergoes three reactions catalyzed by CYP11B2 to become aldosterone. 17alpha-hydroxyprogesterone is created from pregnenolone by using 3-beta-hydroxysteroid dehydrogenase/isomerase. CYP21A2 then hydroxylates 17alpha-hydroxyprogesterone which results in the production of 11-deoxycortisol. CYP11B1 quickly converts 11-deoxycortisol to cortisol. Cortisol is an active steroid hormone, and its conversion to the inactive cortisone has been known to occur in various tissues, with increased conversion occurring in the liver. Pregnenolone is an important hormone as it is responsible for the beginning of the synthesis of many hormones not pictured in this pathway such as testosterone and estrogen. Cortisol receptors are found in almost every bodily cell, so this hormone affects a wide range of body functions. Some of these functions include metabolism regulation, inflammation reduction, regulating blood sugar levels and blood pressure, and helps with the formation of memories.

Steroidogenesis is a process that through the transformations of other steroids, produces a desired steroid. Some of these desired steroids include cortisol, corticoids, testosterone, estrogens, aldosterone and progesterone. To begin the synthesis of steroid hormones, cholesterol synthesizes a hormone called pregnenolone. This is done by cholesterol from the cytosol or lysosome being brought to the mitochondria and becoming fixed in the inner mitochondrial membrane. Once there, the cholesterol becomes pregnenolone through three reactions. The enzyme responsible for catalyzing all three reactions is CYP11A, a side chain cleavage enzyme. After being created, the pregnenolone enters the cytosol, where the cholesterol originated. Once in the cytosol, pregenolone synthesizes progesterone, using two reactions. These two reactions are both catalyzed by an enzyme called 3-beta-hydroxysteroid dehydrogenase/isomerase. The enzyme CYP21A2 then hydroxylates progesterone, which converts it to deoxycorticosterone. Deoxycorticosterone then undergoes three reactions catalyzed by CYP11B2 to become aldosterone. 17alpha-hydroxyprogesterone is created from pregnenolone by using 3-beta-hydroxysteroid dehydrogenase/isomerase. CYP21A2 then hydroxylates 17alpha-hydroxyprogesterone which results in the production of 11-deoxycortisol. CYP11B1 quickly converts 11-deoxycortisol to cortisol. Cortisol is an active steroid hormone, and its conversion to the inactive cortisone has been known to occur in various tissues, with increased conversion occurring in the liver. Pregnenolone is an important hormone as it is responsible for the beginning of the synthesis of many hormones not pictured in this pathway such as testosterone and estrogen. Cortisol receptors are found in almost every bodily cell, so this hormone affects a wide range of body functions. Some of these functions include metabolism regulation, inflammation reduction, regulating blood sugar levels and blood pressure, and helps with the formation of memories.

Steroidogenesis is a process that through the transformations of other steroids, produces a desired steroid. Some of these desired steroids include cortisol, corticoids, testosterone, estrogens, aldosterone and progesterone. To begin the synthesis of steroid hormones, cholesterol synthesizes a hormone called pregnenolone. This is done by cholesterol from the cytosol or lysosome being brought to the mitochondria and becoming fixed in the inner mitochondrial membrane. Once there, the cholesterol becomes pregnenolone through three reactions. The enzyme responsible for catalyzing all three reactions is CYP11A, a side chain cleavage enzyme. After being created, the pregnenolone enters the cytosol, where the cholesterol originated. Once in the cytosol, pregenolone synthesizes progesterone, using two reactions. These two reactions are both catalyzed by an enzyme called 3-beta-hydroxysteroid dehydrogenase/isomerase. The enzyme CYP21A2 then hydroxylates progesterone, which converts it to deoxycorticosterone. Deoxycorticosterone then undergoes three reactions catalyzed by CYP11B2 to become aldosterone. 17alpha-hydroxyprogesterone is created from pregnenolone by using 3-beta-hydroxysteroid dehydrogenase/isomerase. CYP21A2 then hydroxylates 17alpha-hydroxyprogesterone which results in the production of 11-deoxycortisol. CYP11B1 quickly converts 11-deoxycortisol to cortisol. Cortisol is an active steroid hormone, and its conversion to the inactive cortisone has been known to occur in various tissues, with increased conversion occurring in the liver. Pregnenolone is an important hormone as it is responsible for the beginning of the synthesis of many hormones not pictured in this pathway such as testosterone and estrogen. Cortisol receptors are found in almost every bodily cell, so this hormone affects a wide range of body functions. Some of these functions include metabolism regulation, inflammation reduction, regulating blood sugar levels and blood pressure, and helps with the formation of memories.

Steroidogenesis is a process that through the transformations of other steroids, produces a desired steroid. Some of these desired steroids include cortisol, corticoids, testosterone, estrogens, aldosterone and progesterone. To begin the synthesis of steroid hormones, cholesterol synthesizes a hormone called pregnenolone. This is done by cholesterol from the cytosol or lysosome being brought to the mitochondria and becoming fixed in the inner mitochondrial membrane. Once there, the cholesterol becomes pregnenolone through three reactions. The enzyme responsible for catalyzing all three reactions is CYP11A, a side chain cleavage enzyme. After being created, the pregnenolone enters the cytosol, where the cholesterol originated. Once in the cytosol, pregenolone synthesizes progesterone, using two reactions. These two reactions are both catalyzed by an enzyme called 3-beta-hydroxysteroid dehydrogenase/isomerase. The enzyme CYP21A2 then hydroxylates progesterone, which converts it to deoxycorticosterone. Deoxycorticosterone then undergoes three reactions catalyzed by CYP11B2 to become aldosterone. 17alpha-hydroxyprogesterone is created from pregnenolone by using 3-beta-hydroxysteroid dehydrogenase/isomerase. CYP21A2 then hydroxylates 17alpha-hydroxyprogesterone which results in the production of 11-deoxycortisol. CYP11B1 quickly converts 11-deoxycortisol to cortisol. Cortisol is an active steroid hormone, and its conversion to the inactive cortisone has been known to occur in various tissues, with increased conversion occurring in the liver. Pregnenolone is an important hormone as it is responsible for the beginning of the synthesis of many hormones not pictured in this pathway such as testosterone and estrogen. Cortisol receptors are found in almost every bodily cell, so this hormone affects a wide range of body functions. Some of these functions include metabolism regulation, inflammation reduction, regulating blood sugar levels and blood pressure, and helps with the formation of memories.

Stilbenoids are a family of phenylpropanoids which contain a 1,2-diphenylethylene moiety that exist in the plant kingdom and have a variety of biological functions (PMID: 23014926). Diarylheptanoids are another group of phenylpropanoids that are found in plants which have a 1,7-diphenylheptane skeleton (PMID: 21121274). Gingerols are a group of compounds containing a gingerol moiety, some of which are known to be useful for medication purposes (PMID: 26228533). In Arabidopsis, the stilbenoid, diarylheptanoid, and gingerol biosynthesis pathway takes place in the endoplasmic reticulum. This pathway involves coumaroyl-CoA sourced either directly from phenylpropanoid biosynthesis or derived from cinnamoyl-CoA in a reaction catalyzed by cinnamate-4-hydroxylase. Removal of a CoA group from coumaroyl-CoA and a reaction of coumaroyl-CoA with either shikimic acid or quinic acid produces 4-coumaroylshikimic acid or coumaroyl quinic acid. This is catalyzed by hydroxycinnamoyl-CoA shikimate/quinate hydroxycinnamoyl transferase. CYP98A3 enzyme catalyzes hydroxylation of the products to produce caffeoylshikimic acid or chlorogenic acid respectively. Further reaction of products with CoA, catalyzed again by hydroxycinnamoyl-CoA shikimate/quinate hydroxycinnamoyl transferase, produces caffeoyl-CoA. Caffeoyl-CoA is then reacted with S-adenosyl-L-methionine to produce feruloyl-CoA with catalyzation by caffeoyl-CoA O-methyltransferase. 1-dehydro-6-gingerdione and 6-gingerol may then be further derived from feruloyl-CoA.

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

Stiripentol is an antiepileptic agent used in combination with other anticonvulsants to treat seizures associated with Dravet syndrome. Stiripentol is an antiepileptic agent that is an aromatic allylic alcohol drug, which makes it structurally unique from other antiepileptic drugs. The clinical development and marketing of stiripentol were first delayed due to the drug's potent inhibitory effects on hepatic cytochrome P450 (CYP) enzymes. However, its clinical efficacy as adjunctive therapy for epilepsies stems from its inhibitory action on CYP enzymes, as stiripentol reduces the degradation of CYP-sensitive antiepileptic drugs, hence boosting their therapeutic efficacy. The mechanism by which stiripentol exerts its anticonvulsant effect in humans has not been fully elucidated. Possible mechanisms of action include direct effects mediated through the gamma-aminobutyric acid GABAA receptor and indirect effects involving inhibition of cytochrome P450 activity. Stiripentol also improves the effectiveness of many other anticonvulsants, possibly due to its inhibition of certain enzymes, slowing the drugs' metabolism and increasing blood plasma levels. Stiripentol is a positive allosteric modulator of GABAA receptors in the brain that enhances the opening duration of the channel by binding to a site different than the benzodiazepine binding site. It binds to GABAA receptors containing any of the α, β, γ, or δ-subunits but displays the most potent potency when bound to receptors containing α3 or δ subunits. Stiripentol also binds to GABAA receptor-dependent chloride channels via a barbiturate-like mechanism. Stiripentol potentiates GABA transmission by enhancing the release of GABA, reducing synaptosomal uptake of GABA, and inhibiting GABA transaminase-mediated breakdown of GABA. It can be found under the brand name Diatomite and can cause side effects such as tiredness, shaking, coordination issues, and nausea. Stiripentol is administered as an oral tablet.

Streptokinase is a purified, sterile bacterial protein 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. Streptokinase 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 Streptokinase depends on the presence of fibrin. Only small amounts of plasmin is formed from plasminogen when there is no fibrin.