Structural and functional assembly of rat intestinal cytochrome P-450 isozymes. Effects of dietary iron and selenium

We have reported previously that both dietary iron and selenium regulate intestinal cytochrome P-450 content by modulating the synthesis of its prosthetic heme moiety. Whether these elements are required for synthesis and/or viability of its apocytochrome moiety is unknown. We have examined the effects of intraluminal deprivation of these elements on the apocytochrome moieties of the constitutive (P-450) and the beta-naphthoflavone inducible (P-448) intestinal isozymes. The relative content of intestinal apocytochrome P-450 moieties generated by dietary deprivation of iron and/or selenium was assessed indirectly by complexing with exogenous heme in vitro, to reassemble the holocytochromes which could be monitored spectrally and catalytically. We now report that, whereas both intraluminal iron and selenium are required for maintenance of the prosthetic apocytochrome moiety of the constitutive intestinal isozyme, only intraluminal selenium is required for the viability of apocytochrome P-448. The latter apparently survives in the absence of intraluminal iron and can be assembled to the holocytochrome, with exogenously added heme. The mechanistic basis of the critical requirement of intestinal apocytochromes for intraluminal selenium is unclear. It is intriguing, however, that the deleterious effects of selenium deprivation are principally exerted in cell systems actively synthesizing protein and inexorably dependent on their extracellular milieu for their nutriment.