The formation of cytochrome P-450 metabolic intermediate complexes in isolated hepatocytes.

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Title The formation of cytochrome P-450 metabolic intermediate complexes in isolated hepatocytes.
Publication Type dissertation
School or College College of Pharmacy
Department Pharmacology & Toxicology
Author Roberts, Stephen Michael.
Date 1977-12
Description This thesis examines the formation of cytochrome P-450 metabolic intermediate (MI) complexes in isolated hepatocytes. The validity of the model was established, and comparisons were made between MI complex formation in hepatocytes and microsomal suspension derived from untreated and Phenobarbital-pretreated rats. The rates of MI complex formation, the presence of the substrate optimum effect for certain substrates, and the stability of the MI complexes were compared. Information from these comparisons was used in the study of possible mechanisms for inconsistent observation on MI complex formation between microsomes and isolated perfused livers and whole animals. The relationship between substrate concentration and rate of reaction was established for N-hydroxyamphetamine, SKF 525-A and norbenzphetamine in hepatocytes from Phenobarbital-pretreated rats, as well as for N-hydroxyamphetamine and norbenzphetamine in hepatocytes from untreated rats. These relationships will provide a basis for comparison in future studies of MI complex formation in isolated perfused livers. The stability of MI complexes formed in vitro in microsomes was examined, and it was determined that the MI complexes are unstable under conditions. The rates of decay are influenced by temperature, and the degree of influence varies depending on the substrate from which the MI complex is formed. Hepatocytes isolated from drug-treated rats were found to contain similar amounts of MI complex as microsomes from identically treated animals. The implications of the results on possible mechanisms underlying the discrepant in vitro and in vivo observation are discussed.
Type Text
Publisher University of Utah
Subject Pharmacology; Microsomes
Subject MESH Cytochrome P-450 Enzyme System; Hepatocytes
Dissertation Institution University of Utah
Dissertation Name PhD
Language eng
Relation is Version of Digital reproduction of "The formation of cytochrome P-450 metabolic intermediate complexes in isolated hepatocytes." Spencer S. Eccles Health Sciences Library. Print version of "The formation of cytochrome P-450 metabolic intermediate complexes in isolated hepatocytes." available at J. Willard Marriott Library Special Collection. QP 6.5 1977 R62.
Rights Management © Stephen Michael Roberts.
Format application/pdf
Format Medium application/pdf
Identifier us-etd2,175
Source Original: University of Utah Spencer S. Eccles Health Sciences Library (no longer available).
ARK ark:/87278/s6pr89j7
Setname ir_etd
ID 193224
Reference URL https://collections.lib.utah.edu/ark:/87278/s6pr89j7
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