Heme in intestinal epithelial cell turnover, differentiation, detoxification, inflammation, carcinogenesis, absorption and motility

Figure 2 A: Epithelium of the crypt region is active in cell proliferation and differentiation. Heme production is required for the synthesis of heme containing enzymes. In these cells there are also high levels of heme oxygenase activity suggesting that heme breakdown is required for the production of bilirubin and carbon monoxide to maintain appropriate proliferation, differentiation and apoptosis. If the oxygen tension of the cell should increase or production of heme exceeds use, as would be seen as differentiation proceeds, then excess heme may be exported via FLVCR to limit oxidative stress. Increased oxidative stress may also be buffered by the antioxidant bilirubin; B: In the presence of increased oxidative stress caused by excess heme production, impaired FLVCR transport or increased oxygen tension, heme increases to levels that are genotoxic and the cell is predisposed to pro-apototic gene expression placing the cell into a death programme. Normal intestinal growth and differentiation would be impaired.