Involvement of stearoyl-CoA desaturase in the reduction of amidoxime prodrugs.
1. This study investigates the enzymatic reduction of N-hydroxylated amidines by porcine adipose tissue and the possible involvement of stearoyl-CoA desaturase (SCD). 2. The reduction of the model substrate benzamidoxime was studied with porcine adipose tissue microsomes and partially purified SCD from SCD-enriched rat liver microsomes. 3. Inhibitor studies with these microsomal preparations using various inhibitors including anti-SCD antibody, cyanide and stearoyl-CoA supported a role for SCD in the reduction of N-hydroxylated amidines in adipose tissue. The content and activity of SCD in these microsomes was established by Western blot and SCD activity determinations. Additionally, a reconstituted system of cytochrome b(5), NADH-cytochrome b(5) reductase and partially purified SCD from SCD-enriched rat liver microsomes supported benzamidoxime reductase activity that was inhibitable by an anti-SCD antibody. 4. The results support the participation of SCD in the reduction of amidoxime prodrugs and demonstrate for the first time that SCD can also accept foreign compounds (xenobiotics) as substrates.
Reh
R
R
Institute of Pharmacy, Christian-Albrechts-University of Kiel, Kiel, Germany.
Ozols
J
J
Clement
B
B
D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001550:Benzamidines / Q000378:metabolism*; D015153:Blotting, Western; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System; D005260:Female; D008297:Male; D008861:Microsomes / Q000378:metabolism*; D011355:Prodrugs / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013230:Stearoyl-CoA Desaturase / Q000276:immunology / Q000378:metabolism*; D013552:Swine
D000906:Antibodies; D001550:Benzamidines; D065607:Cytochrome P-450 Enzyme Inhibitors; D011355:Prodrugs; C053561:benzamidoxime; D003577:Cytochrome P-450 Enzyme System; C418330:NADH-benzamidoxime reductase; D013230:Stearoyl-CoA Desaturase