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The enzymology of the in–vitro oxidation of prolintane to oxoprolintane
Author(s) -
Whittlesea M. C.,
Gorrod J. W.
Publication year - 1993
Publication title -
journal of clinical pharmacy and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.622
H-Index - 73
eISSN - 1365-2710
pISSN - 0269-4727
DOI - 10.1111/j.1365-2710.1993.tb00603.x
Subject(s) - potassium cyanide , chemistry , aldehyde oxidase , monooxygenase , cytochrome , metabolite , biochemistry , enzyme , microsome , cyanide , oxidase test , cytochrome p450 , xanthine oxidase , organic chemistry
SUMMARY Studies to investigate the location of the enzymes responsible for oxoprolintane formation from prolintane, a sympathomimetic amine which is used to stimulate appetite, are reported. Aldehyde oxidase, cytochrome P–450 and flavin monooxygenase (FMO) inhibitors were used to investigate the process in male rabbit hepatic, 10 000g supernatant preparations. The results suggest that aldehyde oxidase is the soluble enzyme involved in oxoprolintane formation. Microsomal inhibitor studies show that cytochrome P–450, but not FMO, is also involved in prolintane metabolism to oxoprolintane. Results from animals pretreated with cytochrome P–450 inducers implicate cytochrome P–450UA, IIB and IIE in oxoprolintane formation but not the involvement of P–450IA. Experiments which incorporate potassium cyanide in the incubation medium with prolintane and hepatic preparations have led to the detection of a cyano adduct as a new metabolite. These results suggest that an iminium ion intermediate may be involved in oxoprolintane formation.