A kinetic study comparing the light-reversal properties of carbon monoxide inhibition of ethylmorphine, benzphetamine, and 7-ethoxycoumarin dealkylation with those of hydroxylation of 17-hydroxyprogesterone and testosterone.
The light-reversal properties of carbon monoxide (CO) inhibition of the dealkylation of benzphetamine, ethylmorphine, and 7-ethoxycoumarin by microsomes from phenobarbital (PB)-induced rat livers were compared with those of the 6 beta-, 7 alpha-, and 16 alpha-hydroxylations of testosterone by the same rat hepatic microsomes and C-21 hydroxylation of 17-OH progesterone by steer adrenal microsomes. CO inhibited all reactions studied to essentially the same degree. The significant finding was that the dealkylations were reversed most effectively by light of wavelengths between 440 and 445 nm, rather than around 450 nm, the optimal wavelength for steroid hydroxylations. Moreover, the dealkylations required several-fold higher light intensities for equivalent light reversal. These studies suggest that the heme protein-CO complex responsible for dealkylations has a spectrum corresponding to the shape of the pass band of the 445-nm filter, whereas that of the steroid hydroxylations has its light-reversal maximum at 450 nm and appears to be broader. The measurable differences in the light-reversal properties between the monooxygenations of two groups of substrates, (i) dealkylations and (ii) hydroxylations of lipid substrates, furnish biophysical properties that allow a better characterization of microsomal monooxygenases which should be of value in forwarding progress in the study of these systems.
D019326:17-alpha-Hydroxyprogesterone; D015660:7-Alkoxycoumarin O-Dealkylase; D000302:Adrenal Cortex / Q000378:metabolism; D000818:Animals; D002248:Carbon Monoxide / Q000494:pharmacology*; D002417:Cattle; D003577:Cytochrome P-450 Enzyme System; D003640:Dealkylation; D005037:Ethylmorphine-N-Demethylase / Q000037:antagonists & inhibitors*; D006900:Hydroxylation; D006908:Hydroxyprogesterones / Q000378:metabolism*; D007700:Kinetics; D008027:Light; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D010089:Oxidoreductases, N-Demethylating / Q000037:antagonists & inhibitors*; D010105:Oxygenases / Q000037:antagonists & inhibitors*; D010777:Photochemistry; D051381:Rats; D013739:Testosterone / Q000378:metabolism*
D006908:Hydroxyprogesterones; D013739:Testosterone; D019326:17-alpha-Hydroxyprogesterone; D002248:Carbon Monoxide; D003577:Cytochrome P-450 Enzyme System; D010105:Oxygenases; D015660:7-Alkoxycoumarin O-Dealkylase; C019781:benzphetamine N-demethylase; D010089:Oxidoreductases, N-Demethylating; D005037:Ethylmorphine-N-Demethylase