NMR STUDIES OF CELLULAR METABOLISM

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The development of an artificial liver represents a long standing goal of toxicology as well as medicine. Attempts to utilize various bioreactor models have had only moderate success, with systems being relatively short lived and showing poor expression of drug metabolizing enzymes such as cytochrome P450. However, recent advances in the development of stem cell technology have brought this goal considerably closer to reality. We have recently been working with Prof. Lola Reid and Dr. Jeffrey Macdonald at the University of North Carolina to utilize NMR as a non-invasive tool for assessing various metabolic and flow parameters in several hepatic bioreactor model systems. Dr. Reids group has recently developed an antibody screening method that will be used to negatively sort human hepatic progenitors by fluorescent activated cell sorting, allowing enrichment of hepatic progenitor populations. We also recently have been able to demonstrate the feasibility of NMR monitoring of fluorinated xenobiotic metabolism, as well as a number of other metabolic parameters in a commercially available bioreactor. Preliminary NMR studies utilizing a miniature bioreactor that mimics a human liver lobule have also been performed.We have also recently used NMR spectroscopy to understand the physiology and toxicology of borate. These studies involve the analysis of the ternary complex formed from borate, serine, and the enzyme gamma glutamyl transpeptidase. - artificial liver; bioreactor; NMR; propionate; bacterial cell wall; borate; fluorinated xenobiotics