title: Demethylation capacity of human fetal adrenal mitochondrial cytochrome P-450 in vitro.
abstract: OBJECTIVE
  To explore the capacity and characteristics of adrenal mitochondria to metabolize xenobiotics in vitro in human fetus.
  
  
  METHODS
  Subcellular fractions of fetal adrenal were prepared by differential centrifugation. Mitochondrial P-450 system was proved by spectral analyses and SDS-PAGE. The formaldehyde formation contents were measured with Nash reagent.
  
  
  RESULTS
  The erythromycin N-demethylation linearly increased in the protein concentration (1-4 mg)- and incubation time (10-30 min)-dependent manners. A typical concentration-effect relationship appeared with erythromycin 0.067-1 mmol.L-1 and a positive correlation (r = 0.641, P < 0.05) existed between erythromycin N-demethylation and gestation months. The N-demethylation values (nmol.s-1/g protein) of erythromycin (2.7 +/- 0.8), benzfetamine (1.1 +/- 0.5), and aminophenazone (0.9 +/- 0.4) in mitochondria were 89% (P > 0.05), 162% (P < 0.01), and 62% (P < 0.01), respectively, of those in microsomes. There was correlation between mitochondria and microsomes in the N-demethylation of erythromycin (r = 0.708, P < 0.05) and benzfetamine (r = 0.707, P < 0.05). Troleandomycin stimulated erythromycin N-demethylation in adrenal mitochondria as well as in adrenal and liver microsomes in vitro.
  
  
  CONCLUSIONS
  Fetal adrenal mitochondria, with multiple P-450 isoforms and greater capacity of demethylation, play a role in drug-metabolism during fetal development.
authors.affiliation: Department of Pharmacology, Hubei Medical University, Wuhan, China.
authors.forename: H
authors.initials: H
authors.lastname: Wang
authors.forename: R X
authors.initials: RX
authors.lastname: Peng
authors.forename: Y H
authors.initials: YH
authors.lastname: Zhang
authors.forename: J H
authors.initials: JH
authors.lastname: Chen
authors.forename: Q X
authors.initials: QX
authors.lastname: Li
authors.forename: R
authors.initials: R
authors.lastname: Kong
authors.forename: H
authors.initials: H
authors.lastname: Ding
authors.forename: J P
authors.initials: JP
authors.lastname: Yu
mesh_terms: D000311:Adrenal Glands / Q000201:enzymology*; D000632:Aminopyrine / Q000378:metabolism; D001589:Benzphetamine / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004917:Erythromycin / Q000378:metabolism; D005333:Fetus; D005557:Formaldehyde / Q000378:metabolism; D006801:Humans; D008862:Microsomes, Liver / Q000201:enzymology; D008928:Mitochondria / Q000201:enzymology*; D014217:Troleandomycin / Q000494:pharmacology*
chemical_list: D000632:Aminopyrine; D001589:Benzphetamine; D005557:Formaldehyde; D004917:Erythromycin; D003577:Cytochrome P-450 Enzyme System; D014217:Troleandomycin