Demethylation capacity of human fetal adrenal mitochondrial cytochrome P-450 in vitro.
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.
Wang
H
H
Department of Pharmacology, Hubei Medical University, Wuhan, China.
Peng
R X
RX
Zhang
Y H
YH
Chen
J H
JH
Li
Q X
QX
Kong
R
R
Ding
H
H
Yu
J P
JP
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*
D000632:Aminopyrine; D001589:Benzphetamine; D005557:Formaldehyde; D004917:Erythromycin; D003577:Cytochrome P-450 Enzyme System; D014217:Troleandomycin