The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Detoxication of tyramine by the flavin-containing monooxygenase: stereoselective formation of the trans oxime.

In the presence of pig or adult human liver microsomes, tyramine was metabolized to the corresponding trans oxime through the intermediacy of the hydroxylamine. The requisite intermediate, (4-hydroxyphenethyl)hydroxylamine, was retroreduced to tyramine or converted stereoselectively to the trans oxime in the presence of pig or adult human liver microsomes. Studies of the effect of metabolic inhibitors suggested that formation of the trans oxime and retroreduction of the hydroxylamine were largely dependent on NADPH and the flavin-containing monooxygenase (FMO) and cytochrome P450, respectively. The conclusion that FMO was predominantly responsible for trans oxime formation in human liver microsomes was based on the effect of incubation conditions on tyramine N-oxygenation and the observation that cDNA- expressed human FMO3 also N-oxygenated tyramine to give exclusively the trans oxime. The synthetic hydroxylamine and oxime metabolites of tyramine were examined for affinity to human and animal dopamine and serotonin receptors and the human dopamine transporter. For all of the receptors and for the transporter examined, the avidity of the hydroxylamine and oximes was greater than 10 microM and beyond the effective concentration for physiological relevance. The results suggested that tyramine was sequentially N-oxygenated in the presence of pig and human liver microsomes and cDNA-expressed FMO3 to the hydroxylamine and then to the di-N-hydroxylamine that was spontaneously dehydrated to the trans oxime. This may be facilitated by FMO through a nondissociative substrate-enzyme interaction. Based on the biogenic amine receptor or transporter affinity for the hydroxylamine and oxime metabolites of tyramine, N-oxygenation of tyramine by pig or human liver FMO may represent a detoxication reaction that terminates the pharmacological activity of tyramine.[1]


WikiGenes - Universities