INFLUENCE OF SUBSTRATES OF HEPATIC MIXED FUNCTION OXIDASES ON SPIN EQUILIBRIUM OF CYTOCHROME P-450

1980 ◽  
pp. 139-142 ◽  
Author(s):  
I. Jansson ◽  
G.G. Gibson ◽  
S.G. Sligar ◽  
D.L. Cinti ◽  
J.B. Schenkman
Keyword(s):  
Mixed Function Oxidases ◽  
Cytochrome P 450

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 Decreased liver cytochrome P-450 in rats caused by norethindrone or ethynyloestradiol

1977 ◽  
Vol 166 (1) ◽  
pp. 57-64 ◽  
Author(s):  
I N H White ◽  
U Muller-Eberhard
Keyword(s):  
Marked Effect ◽  
Enzyme System ◽  
Time Dependent ◽  
Female Rats ◽  
Liver Cytochrome ◽  
Mixed Function Oxidases ◽  
Green Pigments ◽  
Cytochrome P 450

1. 19-Nor-17alpha-pregna-1,3,5(10)-trien-20-yne-3,17-diol (ethynyloestradiol) or 17beta-hydroxy-19-nor-17alpha-pregn-4-en-20-yn-3-one (norethindrone) but not 17alpha-ethyl-17beta-hydroxy-19-norandrost-4-en-3-one (norethandrolone) caused a time-dependent loss of cytochrome P-450 when incubated in vitro with rat liver microsomal fractions and NADPH-generating systems. 2. The enzyme system catalysing the norethindrone-mediated loss of cytochrome P-450 had many characteristics of the microsomal mixed-function oxidases. It required NADPH and air, and was inhibited by Co. However, it was unaffected by 1 mM-compound SKF 525A. 3. In microsomal fractions from phenobarbitone-pretreated rats the norethindrone-mediated loss of cytochrome P-450 was increased relative to controls. The norethindrone-mediated cytochrome P-450 loss was less pronounced when the animals were pretreated with 3beta-hydroxy-pregn-5-en-2-one 16alpha-carbonitrile (pregnenolone 16alpha-carbonitrile). Pretreatment with 3-methylcholanthrene rendered the animals resistant to the norethindrone effect. 4. Administration in vivo [100mg/kg, intraperitoneally] of norethindrone or ethinyl oestradiol also produced a time-dependent loss of liver cytochrome P-450. Norethandrolone had a similar, though much less-marked, effect. All three steroids lead to an induction of 5-aminolaevulinate synthase and an accumulation of porphyrins in the liver. 5. The loss of cytochrome P-450 and the accumulation of porphyrins in the liver 2 h after the administration of norethindrone to female rats was similar to that seen in males. 6. Rats pretreated with phenobarbitone and given norethindrone or ethynyloestradiol (100mg/kg, intraperitoneally) formed green pigments in their livers. These had characteristics similar to the green pigments produced in the livers of rats after the administration of 2-allyl-2-isopropylacetamide. No green pigments could be extracted from the livers of control rats or those given norethandrolone, oestradiol or progesterone.

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.

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