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)

Comparative N-glucuronidation kinetics of ketotifen and amitriptyline by expressed human UDP-glucuronosyltransferases and liver microsomes.

Like other basic amphiphilic drugs, the (S)-enantiomer of the antiallergic drug ketotifen exhibited biphasic kinetics when it was converted to two isomeric quaternary ammonium-linked glucuronides in human liver microsomes. For (R)-ketotifen this applied when incubations were carried out in the absence of a detergent. Two UDP-glucuronosyltransferases (UGTs) present in human liver, UGT1A4 and UGT1A3, were previously shown to catalyze tertiary amine N-glucuronidation when expressed in HK293 cells. Therefore, the conjugation kinetics of (R)- and (S)-ketotifen were investigated with the two expressed proteins. When homogenates of HK293 cells expressing UGT1A4 were incubated without detergent, N-glucuronidation kinetics were monophasic with K(M) values of 59 +/- 5 microM for (R)- and 86 +/- 26 microM for (S)-ketotifen. In experiments with membranes containing expressed UGT1A3, somewhat higher K(M) values were obtained. These values correspond to the high rather than to the low K(M) components of ketotifen glucuronidation in liver microsomes, the latter exhibiting K(M) values around 2 and 1 microM, respectively, with (R)- and (S)-ketotifen. With amitriptyline as the substrate, N-glucuronidation kinetics in the absence of detergent were biphasic in human liver microsomes and monophasic with a high K(M) value in cell homogenates containing UGT1A4. The results suggest that UGT1A4 and UGT1A3 catalyze high-K(M) N-glucuronidation of tertiary amine drugs, whereas the low-K(M) reaction requires either an alternative enzyme or a special conformation of UGT1A4 or UGT1A3 that can be attained in liver microsomes, but not in HK293 cell membranes.[1]


WikiGenes - Universities