Changes of metabolism and substrate-binding spectrum of emorfazone between immature and mature guinea-pigs

Abstract

1. K_m values for oxidative metabolism at two types of carbon atoms adjacent to nitrogen and oxygen of the morpholino moiety of emorfazone (α- and β-oxygenation) were 1.2 × 10^-2 and 3.0 × 10^-4M in immature male guinea-pigs, and 8.6 × 10^-3 and 2.5 × 10^-4M in mature male guinea-pigs, respectively.

2. V_max values of α- and β-oxygenation were 0.409 and 0.229 μmol/4 nmol cytochrome P-450 in immature male guinea-pigs, and 0.391 and 0.061 μmol/4nmol cytochrome P-450 in mature male guinea-pigs, respectively.

3. Substrate-binding difference spectrum was composed of type I and reverse type I(RI) spectra both in immature and mature animals, but the spectrum pattern was different.

4. The type RI spectrum was predominant in immature animals, but the spectral pattern in mature animals gradually changed from type RI to type I with increase in substrate concentration.

5. α- and β-Oxygenation may be attributed to two kinds of cytochrome P-450 with different affinities, and the proportions of these cytochrome P-450 species and their spin-state change with maturation of guinea-pigs.