Developmental changes in the amount and functional state of UDP-glucuronosyltransferase

The effect of postnatal development on the activity of liver microsomal UDP-glucuronosyltransferase was determined in male Wistar rats between 25 and 200 days of age using p-nitrophenol as aglycone. Enzyme activity (measured at 1.0 mM UDP-glucuronic acid, 0.05 mM p-nitrophenol) decreased 55% between 25 and 88 days of age and was constant thereafter. Treatment of microsomes with palmitoyl-lysophosphatidylcholine, which allows for an estimation of the amount of enzyme, showed approximately a four-fold decrease in enzyme concentration during the same period. This decrease was confirmed by Western blotting of microsomes with anti-UDP-glucuronosyltransferase antiserum. The fact that a nearly four-fold decline in enzyme concentration led to only a 55% decrease in activity indicates that there was an increase in activity per molecule of UDP-glucuronosyltransferase as the concentration of enzyme decreased. Treatment of microsomes with high pressure or detergent caused a greater extent of enzyme activation in microsomes prepared from 25 than 200 day old rats, suggesting that a fraction of the enzyme in older rats was activated in untreated microsomes. Fatty acid analysis of liver microsomal lipids during postnatal development revealed changes in docosahexaenoic acid (22:6) which correlated with levels of UDP-glucuronosyltransferase activity.