Factors involved in the N-oxidation of isomeric aromatic diazines by microsomal preparations

ALTUNTAŞ T., Gorrod J. W.

Drug Metabolism and Drug Interactions, cilt.12, sa.2, ss.117-130, 1995 (Scopus) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 12 Sayı: 2
  • Basım Tarihi: 1995
  • Doi Numarası: 10.1515/dmdi.1995.12.2.117
  • Dergi Adı: Drug Metabolism and Drug Interactions
  • Derginin Tarandığı İndeksler: Scopus
  • Sayfa Sayıları: ss.117-130
  • Anahtar Kelimeler: diazines, enzyme concentration, enzyme kinetics, in vitro metabolism, incubation time, Km, Ks, substrate concentration, Vmax
  • Ankara Üniversitesi Adresli: Evet

Özet

Factors affecting the metabolism of isomeric aromatic diazines in vitro were studied and the conditions which allow maximal metabolism established. The N-oxidation of isomeric diazines was linear with respect to microsomal concentration up to 0.5 g original liver weight per ml using a rabbit microsomal suspension. N-Oxidation was also linear up to between 20–30 minutes depending on substrate studied. The rate of N-oxide production increased with increase in substrate concentration up to about 10 μmol/incubate, after which the rate declined. By using the data obtained the appropriate kinetic factors, Km and Vmax, for the N-oxidation of pyrazine, pyrimidine and pyridazine by rabbit hepatic microsomal preparations were calculated. Spectral binding constants, Ks, of substrates to cytochrome P450 were also calculated and appeared to be related to the Km values. © Freund Publishing House, Ltd. 1995