Sandbox 45673: Difference between revisions

← Older edit Newer edit →

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

Cody J Cubbage, Christian C. Vess, Lindsey Woods, Ahmed Bajuaifer

@@ Line 13: / Line 13: @@
 Finasteride is a 5-alpha reductase inhibitor. There are three isoforms of 5α-reductase, types I, II, and III. While the drug has a higher affinity for the type II enzyme, it also inhibits the function of the type I and no affinity for type III.<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>
-[[Image: Biochem group project.PNG|thumb|left|'''Fig. 1'''. Proposed mechanism of inhibition by Bull et. al. Image shows how the inhibition of 5alpha-reductase is achieved  as Finasteride is used as a substrate to create an enolate intermediate, similar to the one made  during the reduction of testosterone. However, the complex created does not allow for the proton transfer needed to complete the reduction of NADP-Dihydrofinasteride  to Finasteride, because of the change in the carbanion position<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>]]
+[[Image: Biochem group project.PNG|thumb|right|'''Fig. 1'''. Proposed mechanism of inhibition by Bull et. al. Image shows how the inhibition of 5alpha-reductase is achieved  as Finasteride is used as a substrate to create an enolate intermediate, similar to the one made  during the reduction of testosterone. However, the complex created does not allow for the proton transfer needed to complete the reduction of NADP-Dihydrofinasteride  to Finasteride, because of the change in the carbanion position<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>]]
 ==Medical Uses==