title: Inhibition of rat steroid 5 alpha-reductase (isozyme 1) by suramin.
abstract: In this study, we show the inhibition of rat steroid 5 alpha-reductase (isozyme 1) by suramin. The enzyme activity decreased in a dose-dependent manner as suramin concentrations increased with the calculated drug dose required for 50% inhibition (at 5 microM testosterone and 200 microM NADPH) being 13 microM. Suramin showed non-competitive inhibition of 5 alpha-reductase with respect to testosterone (KT1 = 2.4 microM) and competitive inhibition with respect to NADPH (KiNADPH = 220 nM). Furthermore, suramin and NADP+, but not NAD+, protected 5 alpha-reductase from labeling by 2-azido-NADP+, a photoactive probe which has recently been used to identify the NADPH binding domain of 5 alpha-reductase. These results suggest that suramin inhibits rat steroid 5 alpha-reductase (isozyme 1) at the level of NADPH binding to the enzyme.
mesh_terms: D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000378:metabolism; D058891:5-alpha Reductase Inhibitors; D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D008862:Microsomes, Liver / Q000201:enzymology; D009243:NAD / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D010782:Photolysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013498:Suramin / Q000494:pharmacology*; D013739:Testosterone / Q000378:metabolism; D014466:Ultraviolet Rays
chemical_list: D058891:5-alpha Reductase Inhibitors; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D009243:NAD; D013739:Testosterone; D009249:NADP; D013498:Suramin; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase