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The hydrolysis of acetanilide and some of its derivatives by enzymes in the microsomal and soluble fraction prepared from livers of various species

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Summary

The velocity of hydrolysis of some acetanilide derivatives by guinea pig liver microsomes was found to be proportional to the microsome content of the suspension.

Several extractions of the homogenate prepared from the livers of various species were needed for extracting most of the activity located in the soluble and the microsomal fraction.

Acetanilide, p-acetaminophenol, phenacetin, and a ring-substituted phenacetin derivative (compound IX) were used as substrates in measuring the hydrolytic activity in the microsomal and soluble fraction from liver. The ratio between these activities was found to vary widely with the substrate and the species (rabbit, guinea pig, dog, and cat) used. The soluble fractions of all species hydrolyzed acetanilide more rapidly than the microsomes, and the microsomes were more active than the soluble fractions in hydrolyzing the ring-substituted phenacetin derivative.

In a study of the hydrolysis of acetanilide and 12 derivatives by the microsomes prepared from the livers of rabbits, dogs, and guinea pigs the replacement of the N-acetyl residue in phenacetin by α-dimethylamino-β-hydroxybutyric acid was found to decrease the rate of hydrolysis. Substitution of an acetyl, propionyl, or butyryl residue in m-position to the amino group of phenacetin increased the rate of hydrolysis.

N-methyl phenacetin was hydrolyzed more slowly than phenacetin by the soluble fractions prepared from guinea pig's, rabbit's dog's and cat's liver and by the microsomes except those from guinea pigs. The substitution of an N-methyl group in α-dimethylamino-β-hydroxybutyric acid phenetidide produced a compound which was found not to be hydrolyzed by microsomes or soluble fraction from the livers of the 4 species—or so slowly that it could not be detected in our experiments.

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  1. Pharmakologisches Institut der Universität München, Germany

    Manfred Kiese & Gerhard Renner

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  1. Manfred Kiese
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  2. Gerhard Renner
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Kiese, M., Renner, G. The hydrolysis of acetanilide and some of its derivatives by enzymes in the microsomal and soluble fraction prepared from livers of various species. Naunyn - Schmiedebergs Arch 252, 480–500 (1966). https://doi.org/10.1007/BF00258646

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  • DOI: https://doi.org/10.1007/BF00258646

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