Abstract
The regulation of glucuronidation during hypoxia was studied in isolated hepatocytes by analysing the dependence of acetaminophen glucuronidation rate on the intracellular concentrations of UTP, glucose 1-phosphate, UDP-glucose and UDP-glucuronic acid. The steady-state concentrations of these metabolites in cells from fed and starved rats were altered by exposure to various hypoxic O2 concentrations and by adding exogenous glucose. Changes in glucuronidation rate under all conditions were explained in terms of the concentrations of the substrates for UDP-glucose pyrophosphorylase, i.e. UTP and glucose 1-phosphate. Steady-state rates for the UDP-glucose pyrophosphorylase reaction, calculated by using published kinetic constants and measured glucose 1-phosphate and UTP concentrations, were in agreement with the measured glucuronidation rates. Thus the UDP-glucose pyrophosphorylase reaction is the key regulatory site for drug glucuronidation during hypoxia. Control at this site indicates that glucuronidation in vivo may be generally depressed in pathological conditions involving hypoxia and energy (calorie) malnutrition.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
