James Rusling and co-workers at the University of Connecticut have combined for the first time human liver cytosol and microsomes as enzyme sources for screening multi-enzyme metabolic processes.   Rusling explains that this work has potential importance in the drug discovery and development industries.   'Toxicity issues defeat about 30% of all drugs at the clinical trial stage, after all the in vitro tests have been used.'   This work could potentially alleviate that problem by catching toxic metabolites before the clinical trial stage.  

The array spots contain an electrochemiluminescent ruthenium polymer, DNA, human liver cytosol and microsomes assembled on a graphite chip.   Compounds known to have toxic pathways were tested, for example ethylene dibromide.   When a compound is introduced into the system, one or more of the enzymes present react either through oxidation or bioconjugation to produce the metabolite.   This then interacts with the DNA making it more vulnerable to oxidation by the ruthenium polymer, resulting in an increase in the electrochemiluminescense which is then measured.  

Rusling says that 'we are working toward denser arrays with even more metabolic enzymes represented, and would like to see this technology, along with its nanoparticle-based LC-MS companion technology employed in industrial research such as the drug industry.'   However, the challenge at the moment, is that 'although the technology is simple and inexpensive, it is not commercialised and therefore cannot be bought off the shelf,' explains Rusling.

Mary Badcock