The effect of dietary protein quantity on the activity of UDP-glucuronyltransferase and its physiological significance in drug metabolism.

Low dietary protein has been shown to induce the activity of rat hepatic UDP-glucuronyltransferase (UDPGTase) as measured in vitro. The assay of UDPGTase in vitro is hampered by the need to solubilize the microsomal membrane, without destroying the physiological significance of the measurements. The present work was to determine the effect of dietary protein on the activity of UDPGTase and on the activity of UDP-glucose dehydrogenase. Chloral hydrate induced sleeping time was used as a bioassay for UDPGTase, confirming the physiological significance of the in vitro analysis. Sixty male rats were maintained on three different protein levels (7.5, 15, and 45%) for 16 days. Fifteen rats from each group were sacrificed and hepatic UDPGTase, cytochrome P-450, UDP-glucose dehydrogenase, and alcohol dehydrogenase were assayed. Five rats from each group were dosed with 7.5% chloral hydrate (4.8 mL/kg body weight) to measure sleeping time. Rats on 7.5% dietary protein had significantly higher UDPGTase activity than rats fed either 15 or 45% protein diets. These differences in enzyme activity in vitro correlated with the differences in chloral hydrate sleeping time. Dietary protein was not found to affect the activity of UDP-glucose dehydrogenase as measured in vitro.