Effect of dietary protein on hepatic and extrahepatic phase I and phase II drug metabolizing enzymes

Weanling male rats were fed low (LP, 7.5%), standard (SP, 15%) or high protein (HP, 45%) diet for 7 or 14 days ad libitum, and cytochrome c reductase (CYC) and UDP-glucuronosyltransferase (UGT) enzyme activities were determined in intestine, kidney and liver microsomes. HP diet increased CYC activity in intestine and kidney, while LP diet bad no effect. Hepatic CYC activity declined with decreasing level of dietary protein. Liver and intestine UGT activities were higher on an LP diet, while kidney enzyme activities were higher on an HP diet. UGT activity toward a-naphthol, a UGT1 isoform substrate, was modulated by dietary protein in all tissues, while UGT activity toward 4-hydroxybiphenyl, a substrate for a second UGT1 isoform, was affected only in the intestine. The duration of feeding affected CYC and UGT activities in the intestine. This observation may be explained by the dynamic nature of intestinal tissue. The observation of unique tissue and enzyme responses suggests that generalizations regarding metabolic response to diets based on hepatic studies or single enzymes, may be erroneous.