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Studies on the Interaction of Anutrients of Endoplasmic Reticulum Mixed Function Oxidases.

Al-Gailany, Kais Atwan Sharief. (1975) Studies on the Interaction of Anutrients of Endoplasmic Reticulum Mixed Function Oxidases. Doctoral thesis, University of Surrey (United Kingdom)..

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Abstract

The structural requirements for the type I, Reverse type I and type II microsomal cytochrome P-450 binding sites have been studied using several series of organic compounds which contain restricted numbers of functional groups. The binding affinity of a type I spectral change produced by series of saturated and aromatic hydrocarbons, fatty acids, methyl esters, alkyl-p-nitro-phenylethers and aliphatic carbamates appears to correlate directly with their octanol/aqueous solution partition coefficients indicating that hydrophobic binding is the prime requirement for type I binding. l-Anilino-8-Naphthalene sulphonate and the novel fluorescent probes(+) and(-) Warfarin, Benzidine and 7,12-Dimethylbenzanthracene, together with difference spectra, have been used to further investigate the nature of the hepatic microsomal cytochrome P-450 binding sites. The type I and Reverse type I sites have both confirmed as being associated, with a hydrophobic environment, and these binding interactions are mutually exclusive whereas the type II site is in a hydrophilic region. A study of the cytochrome P-450 mediated O-dealkylation of four p-nitrophenylalkylethers and two a-aeuterated alkyl-p-nitro-phenylethers indicated a complex relationship between type I binding and metabolism. The initial dealkylation rates were in the order p-nitrophenylisopropylether >p-nitrophenylbutylether >p-nitro-phenylethylether >p-nitrophenylmethylether > a-D2 p-nitrophenyl-ethylether > a-D3 p-nitrophenylmethylether. A free radical mechanism of oxidation is proposed to explain this sequence.

Item Type: Thesis (Doctoral)
Divisions : Theses
Authors : Al-Gailany, Kais Atwan Sharief.
Date : 1975
Additional Information : Thesis (Ph.D.)--University of Surrey (United Kingdom), 1975.
Depositing User : EPrints Services
Date Deposited : 24 Apr 2020 15:27
Last Modified : 24 Apr 2020 15:27
URI: http://epubs.surrey.ac.uk/id/eprint/855086

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