The effect of membrane lipid hydrogenation on drug metabolising activity

A range of monometallic Pd-PVP(Poly(2-vinylpyrrolidone) and bimetallic PdRh-PVP catalysts, of different molecular weights were synthesized, for the catalytic hydrogenation of double bonds within the membranes of biological systems. The use of these catalysts would therefore allow investigation as to whether the unsaturated nature of membrane fatty acids does have a role in determining cytochrome P450 activity. The catalysts were hydrogenated with crotonic acid (0.25M), linoleic acid (0.025M), phosphatdylcholine (PC) (1mg/mi) and finally with microsomal fractions at a concentration of I mg/mI. It was found that PdRh-PVP was the more effective catalyst when hydrogenated with crotonic and linolieic acid, therefore it was decided that the bimetallic PdRh-PVP catalyst would be used for the hydrogenation of PC and microsomes. The extent of hydrogenation was determined using gas chromatography (GC). GC traces of linoleic acid samples showed evidence of hydrogenation occurring through the presence of saturated forms namely oleate and stearate. The GC trace of PC revealed that hydrogenation took place with longer chained fatty acids such as arachidonic acid. A similar effect was observed with the microsomes, except following hydrogenation a decrease of approximately 50% in the actual amount of arachidonic acid was observed. Cytochrome P450 activity was measured using alkoxyresorufins as probe substrates. It was found that hydrogenation of microsomes caused a decrease in the metabolism of benzyloxyresorufin O-dealkylase (BROD) but an increase of metabolism pentoxyresorufin O-dealkylase (PROD) was seen. The use of these catalysts together with the technique of catalytic hydrogenation provided an appropriate method of investigating the effect of membrane fatty acid unsaturation on drug metabolising activity.

Name dc:type.qualificationname

msc

Level dc:type.qualificationlevel

masters

Grantor dc:publisher.institution

University of Central Lancashire

Year dc:date.issued

2002

Author dc:creator

• Cheng, Susannah

• F410 - Forensic science

Language dc:language

en