II. Role of the Type I Drug-Binding Site of Cytochrome P-450

tide synergism 0 of time reduced triphosphmopyridine miucleotide-dependent mixed-function oxidase system of hiepatic microsomes. II. Role of time type I drug-binding site of cyto-chrome P-450. JIol. Pliarmacol. 9, 470-485 (1973); Studies of the I)PXH synergism of time TPNH-depemmdemmt mixed-function oxidase system of huepatic m-r-iicroscomes usiumg a variety ef substrates revealed that synergism occurred when the subst rat (‘5 were tyJ)e I bimiding cc ompe)UIidS (amimiopyrimme, benzphetanmine, codeimne, ethyl-mmio)rpimitno’, miorcodeine), but DOt wheim the substrtites we-re type- II binding compounds (amuilimmc-. p-chmloro-N-metlmylammihimme). Time role of type I binding in I)PXH synergism of drug uiieta-bohisun was invc-st-igated by employing microsomes which vtiried in their abilities to j)roducc ’ tt t\’j)e I bimiding spectrum with ethylmorpliine. This was ticcomplished by selecting micruos(omc’s from different- tiumimal source-s (male rats of different ages, female rats, 3-methyl cholammthmre-ume-treated rtits) omr by subjecting micro&4omes from a givemi source to treatments knowim too diminish t\’pe ’ I bindimmg (treatment with SKF 525-A or with phosphohipase C, storage-). Usiimg etimylmorpimine as thme substrate, type I binding as showmm too be directly correlated vit-lm T)PXH syumo-rgisnm an(1 with DPNH utihizatiomm. Time- mean ratio of DPN