Membrane bound cytochrome P-450 determines the optimal temperatures of NADPH-cytochrome P-450 reductase and cytochrome P-450-linked monooxygenase reactions in rat and trout hepatic microsomes.

The hepatic monooxygenase systems largely responsible for the biotransformation of drugs and other xenobiotics are comprised of NADPH-cytochrome P-450 reductase and multiple forms of cytochrome P-450. Optimal temperatures for these systems in the trout and rat are 26 degrees and 37 degrees, respectively. Purified trout and rat reductases are optimally functional at 26 degrees and 37 degrees, respectively, when added to trout and rat microsomes. However, rat reductase was shown to function optimally at 26 degrees when added to trout microsomes and trout reductase functioned optimally at 37 degrees when added to rat microsomes. Corresponding shifts in optimal temperatures of cytochrome P-450-linked 0-deethylation of 7-ethoxycoumarin occurred when these reductases were added to rat or trout microsomes. It is proposed that the phospholipid annulus surrounding the active site of membrane-bound cytochrome P-450 determines the optimal temperature of cytochrome P-450 systems.