scholarly journals Changes in certain kinetic properties of hepatic microsomal aniline hydroxylase and ethylmorphine demethylase associated with postnatal development and maturation in male rats

1969 ◽  
Vol 113 (4) ◽  
pp. 681-685 ◽  
Author(s):  
Theodore E. Gram ◽  
Anthony M. Guarino ◽  
David H. Schroeder ◽  
James R. Gillette
Keyword(s):  
Enzyme Activity ◽  
Postnatal Development ◽  
Male Rats ◽  
Kinetic Properties ◽  
Michaelis Constant ◽  
Microsomal Cytochrome ◽  
Aniline Hydroxylase ◽  
Mixed Function Oxidases ◽  
Demethylase Activity ◽  
Cytochrome P 450

1. Changes in certain kinetic properties (Vmax. and apparent Km) of hepatic microsomal mixed-function oxidases have been studied as a function of postnatal development and maturation in male rats. 2. Microsomal cytochrome P-450 content changed only slightly between 1 and 12 weeks of age. 3. Aniline hydroxylase activity (Vmax.) increased abruptly between 1 and 2 weeks of age to greater than adult activities and then returned to a plateau value between 4½ and 12 weeks of age. Ethylmorphine demethylase activity remained low and relatively constant between 1 and 3 weeks of age and then increased markedly (∼100%) between 3 and 4½ weeks. 4. The apparent Michaelis constant (Km) for aniline hydroxylation increased almost linearly with time between 1 and 6 weeks of age and tended to reach a plateau value thereafter. The apparent Km for ethylmorphine demethylation increased between 1 and 3 weeks of age and then decreased abruptly to a constant value between 6 and 12 weeks. 5. The data indicate that developmental changes in the activity of these microsomal oxidases do not correlate temporally with each other or with changes in microsomal cytochrome P-450 content. 6. The most dramatic changes in enzyme activity were associated with early development (1–3 weeks) and weaning (3–4 weeks). 7. Changes in weight of seminal vesicle, a criterion of sexual maturation in male rats, were most prominent between 6 and 8 weeks of age and thus appeared to be separated in time from the prominent changes in enzyme activity.

scholarly journals Postnatal development and sublobular distribution of cytochrome P-450 in rat liver: a microphotometric study.

1993 ◽  
Vol 41 (3) ◽  
pp. 397-400 ◽  
Author(s):  
J Watanabe ◽  
Y Asaka ◽  
S Kanamura
Keyword(s):  
Postnatal Development ◽  
Rat Liver ◽  
Perinatal Period ◽  
Postnatal Growth ◽  
Male Rats ◽  
Heterogeneous Distribution ◽  
Liver Lobule ◽  
Subsequent Period ◽  
The Difference ◽  
Cytochrome P 450

To study the process of expression of cytochrome P-450 (P-450) in hepatocytes during development, we measured microphotometrically the P-450 content in periportal and perivenular hepatocytes of male rats during peri- and postnatal growth. From Day 19 of gestation to Day 5 after birth, P-450 content in both periportal and perivenular hepatocytes increased markedly (periportal 1046%; perivenular 819%). The content in periportal hepatocytes remained unchanged from 5 to 20 days of age, and increased slightly (24%) from 20 to 45 days of age. However, the content in perivenular hepatocytes increased progressively (105%) between 5 and 45 days of age. The difference in P-450 content became apparent between periportal and perivenular hepatocytes after 7 days of age. The content in periportal or perivenular hepatocytes reached the adult level at 45 days of age. Therefore, the perinatal period is the time at which a marked increase in P-450 occurs in hepatocytes throughout the liver lobule. The subsequent period before weaning is the time at which the sublobular heterogeneous distribution of P-450 appears. The period after weaning is the time at which a slight increase in P-450 content in periportal hepatocytes and a marked increase in the enzyme in perivenular hepatocytes takes place.

scholarly journals Studies on the substrate-binding sites of liver microsomal cytochrome P-448

1982 ◽  
Vol 207 (1) ◽  
pp. 51-56 ◽  
Author(s):  
C E Phillipson ◽  
C Ioannides ◽  
M Delaforge ◽  
D V Parke
Keyword(s):  
Binding Site ◽  
Binding Sites ◽  
Substrate Binding ◽  
Liver Microsomes ◽  
Substrate Specificities ◽  
Microsomal Cytochrome ◽  
Mixed Function Oxidases ◽  
Substrate Binding Sites ◽  
Cytochrome P 450

The interaction of substrates of the microsomal mixed-function oxidases with cytochromes P-450 and P-448 was investigated by using liver microsomes from rats pretreated with phenobarbital or 3-methylcholanthrene, and with purified forms of the cytochromes isolated from rabbit liver. The two forms of the cytochrome have different substrate specificities; cytochrome P-450 has one type 1 substrate-binding site that can accommodate a large variety of substrates, but in contrast cytochrome P-448 may possess two type 1 substrate-binding sites, one of which is different to that of cytochrome P-450 in that it shows a specificity for substrates such as safrole and 9-hydroxy-ellipticine. These findings explain why the two forms of the cytochrome have different substrate specificities and play contrasting roles in the activation and deactivation of xenobiotics.

scholarly journals Growth hormone and drug metabolism. Acute effects on microsomal mixed-function oxidase activities in rat liver

1976 ◽  
Vol 154 (2) ◽  
pp. 433-438 ◽  
Author(s):  
J T. Wilson ◽  
T C. Spelsberg
Keyword(s):  
Growth Hormone ◽  
Drug Metabolism ◽  
Rat Liver ◽  
Oxidase Activity ◽  
Male Rats ◽  
Mixed Function Oxidase ◽  
Liver Growth ◽  
Mixed Function Oxidases ◽  
Cytochrome P 450 ◽  
Mixed Function Oxidase Activity

Adult male rats were subjected either to sham operation or to hypophysectomy and adrenalectomy and maintained for a total of 10 days before treatment with growth hormone. Results of the early effects of growth hormone on the activities of the mixed-function oxidases in rat liver over a 96h period after growth-hormone treatment are presented. 2. Hypophysectomy and adrenalectomy result in decreased body and liver weight and decreased drug metabolism (mixed-function oxidases). Concentrations of electron-transport-system components are also decreased. 3. In the hypophysectomized/adrenalectomized rats, growth hormone decreases the activities of the liver mixed-function oxidases and the cytochrome P-450 and cytochrome c reductases, as well as decreasing the concentration of cytochrome P-450 compared with that of control rats. Similar but less dramatic results are obtained with sham-operated rats. 4. It is concluded that whereas growth hormone enhances liver growth, including induction of many enzyme activities, it results in a decrease in mixed-function oxidase activity. Apparently, mixed-function oxidase activity decreases in liver when growth (mitogenesis) increases.

scholarly journals The effects of carbon disulphide on rat liver microsomal mixed-function oxidases, in vivo and in vitro

1980 ◽  
Vol 188 (1) ◽  
pp. 107-112 ◽  
Author(s):  
Maria J. Obrebska ◽  
Peter Kentish ◽  
Dennis V. Parke
Keyword(s):  
Rat Liver ◽  
Oxidase Activity ◽  
Carbon Disulphide ◽  
Intraperitoneal Administration ◽  
Male Rats ◽  
Type I ◽  
Mixed Function Oxidase ◽  
Mixed Function Oxidases ◽  
Cytochrome P 450 ◽  
Mixed Function Oxidase Activity

An intraperitoneal dose of CS2 (500mg/kg) to male rats resulted in loss of liver microsomal mixed-function-oxidase activity (85% loss of biphenyl 4-hydroxylase), followed by denaturation of liver cytochrome P-450 to cytochrome P-420, and degradative loss of both cytochromes (50% loss). Losses of NADPH–cytochrome c reductase (20%) and cytochrome b5 were considerably less. Intraperitoneal administration of CS2 (100mg/kg) to rats pretreated wtih phenobarbitone or 3-methylcholanthrene resulted in similar losses, but the rate of destruction was greater with cytochrome P-450 than with cytochrome P-448. At 12h after intraperitoneal injection of CS2 to non-pretreated rats, a new cytochrome (P-448) appeared. Rat liver microsomal preparations incubated with CS2 in the presence of NADPH and O2 resulted in loss of cytochrome P-450 and mixed-function-oxidase activity directly related to the concentration of CS2 (10–100μm) and to the period of incubation. Addition of EDTA (1mm) completely inhibited this destruction of cytochrome P-450 by CS2in vitro. Addition of CS2 to liver microsomal preparations resulted in moderate increases in the Ks values for type-I or type-II substrates, but these were insufficient to account for the inhibition of the mixed-function oxidases. We therefore suggest that desulphuration of CS2 leads to binding of the S to cytochrome P-450, denaturation of cytochrome P-450 to cytochrome P-420, and ultimately to destruction of these cytochromes by autoxidation.

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