Sandbox 45673: Difference between revisions
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==Mechanism== | ==Mechanism== | ||
Finasteride is a 5-alpha reductase inhibitor. There are three isoforms of the 5alpha-reductase enzyme, type I and II, and while the drug has a higher affinity for the type II enzyme, it also inhibits the function of the type I.<ref name="four"> Schieck, Cynthia L.(1998, August) "Finasteride (Propecia ®)". http://www.chm.bris.ac.uk/motm/finasteride/Finasteride%20(Propecia)%20-%20Feature%20Molecule.htm </ref> | Finasteride is a 5-alpha reductase inhibitor. There are three isoforms of the [[5alpha-reductase]] enzyme, type I and II, and while the drug has a higher affinity for the type II enzyme, it also inhibits the function of the type I.<ref name="four"> Schieck, Cynthia L.(1998, August) "Finasteride (Propecia ®)". http://www.chm.bris.ac.uk/motm/finasteride/Finasteride%20(Propecia)%20-%20Feature%20Molecule.htm </ref> | ||
Typically 5α-redcutase turns testosterone into Dihydrotestosterone(DHT), but the enzyme will accept Finasteride as an alternate substrate; turning it into dihydrofinasteride through an enzyme bound, NADP-dihydrofinasteride adduct. Finasteride is similar in structure to testosterone and 5alpha-reductase has almost the same affinity for both molecules. However, Finasteride , having a high affinity for 5α-reductase, covalently binds to the enzyme as a Michael acceptor, through a functionally irreversible reaction. However, the NADP-dihydrofinasteride complex breaks down with a half life of about 1 month at 37˚C., which is why patients must continue taking the drug.<ref name="five"> Bull, Herbert G.*Garcia-Calvo,Margarita Andersson,Stefan†, Baginsky, Walter F.,Chan,H. Karen,Ellsworth,‡ Dina E., Miller,§ Randall R., Stearns,Ralph A.,Bakshi,Raman K.,Rasmusson, Gary H.,Tolman,Richard L., Myers,Robert W.,Kozarich,John W.,Harris,Georgianna S. (1995, August 6) Mechanism-Based Inhibition of Human Steroid 5R-Reductase by Finasteride: Enzyme-Catalyzed Formation of NADP-Dihydrofinasteride, a Potent Bisubstrate Analog Inhibitor. http://pubs.acs.org/doi/pdf/10.1021/ja953069t</ref> | Typically 5α-redcutase turns testosterone into Dihydrotestosterone(DHT), but the enzyme will accept Finasteride as an alternate substrate; turning it into dihydrofinasteride through an enzyme bound, NADP-dihydrofinasteride adduct. Finasteride is similar in structure to testosterone and 5alpha-reductase has almost the same affinity for both molecules. However, Finasteride , having a high affinity for 5α-reductase, covalently binds to the enzyme as a Michael acceptor, through a functionally irreversible reaction. However, the NADP-dihydrofinasteride complex breaks down with a half life of about 1 month at 37˚C., which is why patients must continue taking the drug.<ref name="five"> Bull, Herbert G.*Garcia-Calvo,Margarita Andersson,Stefan†, Baginsky, Walter F.,Chan,H. Karen,Ellsworth,‡ Dina E., Miller,§ Randall R., Stearns,Ralph A.,Bakshi,Raman K.,Rasmusson, Gary H.,Tolman,Richard L., Myers,Robert W.,Kozarich,John W.,Harris,Georgianna S. (1995, August 6) Mechanism-Based Inhibition of Human Steroid 5R-Reductase by Finasteride: Enzyme-Catalyzed Formation of NADP-Dihydrofinasteride, a Potent Bisubstrate Analog Inhibitor. http://pubs.acs.org/doi/pdf/10.1021/ja953069t</ref> | ||