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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 267 (1970), S. 307-326 
    ISSN: 1432-1912
    Keywords: Enzyme Induction ; Microsomal Enzymes ; Michaelis Constants ; Spectral Dissociation Constants ; Affinity for Oxygen and Carbon Monoxide ; Schlüsselwörter ; Enzyminduktion ; Mikrosomale Enzyme ; Michaelis-Konstanten ; Spektrale Dissoziationskonstanten ; Sauerstoff- und Kohlenmonoxid-AffinitÄt
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Phenobarbital treatment of rabbits was found to cause significant changes in some of the apparent Michaelis (K M) constants for p- and N-hydroxylation of aniline [reactions 1 and 2, resp.] and de-ethylation, p- and N-hydroxylation of N-ethylaniline [reactions 3,4, and 5, resp.], and in the spectral dissociation constants (K s) for aniline, N-ethylaniline and ethylisocyanide in isolated hepatic microsomes. The “critical” oxygen concentrations were increased in all reactions investigated. The distribution constants (K G) for CO, determined according to Warburg, decreased in the reactions 2, 3, and 4, and increased in reaction 1. Reaction 5 was not inhibited by CO in microsomes from untreated rabbits and was stimulated by CO after phenobarbital treatment of the animals. Depending on the reaction, theK M-values for aniline and N-ethylaniline were increased, decreased, or remained unchanged by the phenobarbital treatment of the animals. The most striking changes inK M-values were observed with the reactions 2 and 5 in which cytochrome P-450 is either not involved or is not a limiting factor. TheK s-value for ethylisocyanide measured after addition of dithionite to microsomes was increased. The correspondingK s-value measured without dithionite under aerobic conditions remained unchanged. TheK s value for aniline was decreased by the phenobarbital treatment of the animals. Using microsomes from untreated animals theK s value for N-ethylaniline could not be determined exactly. The order of magnitude of this value, however, was greater than that of the corresponding value from phenobarbital-treated animals. The observed alterations in affinity imply that induction by phenobarbital may be associated withqualitative as well as quantitative changes in the hepatic microsomal enzymes or membranes. The qualitative changes could be important for the accessibility of the reacting groups and/or substrate guiding.
    Type of Medium: Electronic Resource
    Library Location Call Number Volume/Issue/Year Availability
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 267 (1970), S. 265-277 
    ISSN: 1432-1912
    Keywords: Enzyme Induction ; Microsomal Hydroxylases ; Cytochrome P-450 ; Progesterone Metabolism ; Enzyminduktion ; Mikrosomale Hydroxylasen ; Cytochrom P-450 ; Progesteron-Stoffwechsel
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The transformation of progesterone into four more polar metabolites was investigated using liver microsomes from untreated as well as phenobarbitaltreated rabbits. The formation of the four metabolites was dependent on oxygen and NADPH. The reactions were inhibited by CO and this inhibition by CO was partially reversible by light. The four reactions had the same pH-optimum at 7.4. The metabolite pattern was not changed by reducing the oxygen pressure, by inhibiting the reactions with CO, by diminishing the CO effect by light, by variation of the pH value, by separating microsomes into smooth and rough membranes, or by increasing the specific enzyme activities by a factor of 1.5, as a result of treating the microsomes by freezing, thawing, and consecutive centrifugation or filtration on agarose gel. Phenobarbital-treatment of the animals increased the formation of the four metabolites to different degrees, i.e. 3, 1.4, 15, and 6 fold, respectively. Since this procedure was the only one which changed the metabolite pattern, this effect is easier to explain by effects of the phenobarbital-treatment on the rate-limiting steps of the four reactions than by the assumption of four different enzymes catalyzing the metabolism of progesterone.
    Type of Medium: Electronic Resource
    Library Location Call Number Volume/Issue/Year Availability
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