Riboflavin cofactor saturation of the cytochrome P450 system

Abstract

Phenobarbital induction of the hepatic microsomal cytochrome P450 system in adult male rats resulted in two-fold increases in cytochrome P450 concentration and NADPH — cytochrome P450 reductase activity over untreated control rats in a two week experiment. Hepatic cytosolic glutathione transferase activity also increased. In animals taking unrestricted dietary riboflavin, the aim was to see if the increased demand for flavin cofactors imposed by induction led to a relative or non-dietary riboflavin deficiency. This was monitored by three vitamin status tests. Erythrocyte riboflavin concentration was similar in untreated and treated groups (7.5 μg per 100 ml erythrocytes), and the erythrocyte glutathione reductase test with cofactor FAD stimulation indicated similar B2 status in treated rats. However, hepatic cytosolic glutathione reductase activity was doubled in the induced animals (to 10.98±0.54 mmol NADPH oxidized per g protein per hour), and was fully saturated with cofactor in both animal groups. Glutathione reductase was also induced by phenobarbital and the enzyme was satisfying a biological role to supply reduced glutathione, for conjugation by glutathione transferase. It is proposed that the increased hepatic demand for flavin cofactors during induction was not being met by riboflavin from erythrocytes or from hepatic glutathione reductase and NADPH cytochrome P450 reductase.