Effects of protein malnutrition on liver cytochrome P450s

Microsomal cytochrome P450s (CYPs) are the key enzymes that control the rate of drag metabolism. In turn, hepatic drag biotransformation is influenced by dietary macronutrients. We examined the effects of protein malnutrition on hepatic CYP1A and 3A in rats. Weanling male rats were fed protein-restricted diets with either 0.5% or 1.0% lactalbumin for 13 weeks. Control rats were fed similar diets but with 18% lactalbumin. Severe protein malnutrition resulted in rats fed the 0.5% and 1.0% lactalbumin diets as evidenced by stunting of growth, lowering of hematocrit and plasma albumin concentrations. Protein malnourished rats had a reduction in their hepatic microsomal concentrations only when expressed as per gm tissue but not as per protein concentration. Western blot analyses showed that protein malnutrition had no effect on hepatic CYP1A1 and only effected CYP1A2 at the most severe conditions (ie. in rats fed the 0.5% lactalbumin diet). Protein malnutrition however, led to >50% reduction in hepatic microsomal CYP3A proteins. Liver microsomal steroid metabolizing enzyme activities were evaluated by quantitation of specific metabolites formed following incubation with 4- C¹⁴ progesterone and TLC separation. Protein malnutrition led to reductions in both 6β- and 16 α-progesterone hydroxylase, but did not affect either 17α-hydroxylase or 5α-reductase activity. Protein malnutrition, thus, modulates the various CYPs differently. Such changes in hepatic CYP concentrations might he the cause of altered drag metabolism accompanying protein malnutrition.