Metabolism of paraldehyde to acetaldehyde in liver microsomes. Evidence for the involvement of cytochrome P-450.
A concentration-dependent acetaldehyde (AcH) generation was observed when paraldehyde was incubated with the mouse liver microsomal fraction. The process, which exhibited a requirement for oxygen and NADPH and was inhibited by carbon monoxide, was found to have a Km of 17.9 mM with respect to paraldehyde and a Vmax of 40.1 nmoles/mg protein/min with respect to AcH formation. NADH was much less effective as an electron donor than NADPH, though a more than additive increase in AcH generation was observed when both of these nucleotides were added to the incubation. The rate of microsomal AcH generation from paraldehyde was increased 2.5-fold by pretreatment of the mice with phenobarbital but only 0.6-fold by pretreatment with 3-methylcholanthrene. Pretreatment with 2-diethylaminoethyl-2,2-diphenylvalerate hydrochloride (SKF-525A) resulted in 54% inhibition of the reaction rate. Addition of metopirone to the incubation inhibited AcH generation in a concentration-related fashion, the inhibition being greatest, proportionately, in microsomes from phenobarbital-pretreated animals. The above results conclusively indicate the involvement of cytochrome P-540 mixed function oxidase in the formation of AcH from paraldehyde by mouse liver microsomes. It is also postulated that this process may be accomplished in the reaction analogous to O-dealkylation.
D000079:Acetaldehyde / Q000096:biosynthesis*; D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008862:Microsomes, Liver / Q000378:metabolism*; D009249:NADP / Q000378:metabolism; D010105:Oxygenases / Q000378:metabolism; D010242:Paraldehyde / Q000378:metabolism*
D009249:NADP; D003577:Cytochrome P-450 Enzyme System; D010105:Oxygenases; D000079:Acetaldehyde; D010242:Paraldehyde