Intestinal absorption of hemoglobin iron-heme cleavage by mucosal heme oxygenase.
Hemoglobin and myoglobin are a major source of dietary iron in man. Heme, separated from these hemoproteins by intraluminal proteolysis, is absorbed intact by the intestinal mucosa. The absorbed heme is cleaved in the mucosal cell releasing inorganic iron. Although this mucosal heme-splitting activity initially was ascribed to xanthine oxidase, we investigated the possibility that it is catalyzed by microsomal heme oxygenase, an enzyme which converts heme to bilirubin, CO, and inorganic iron. Microsomes prepared from rat intestinal mucosa contain enzymatic activity similar to that of heme oxygenase in liver and spleen. The intestinal enzyme requires NADPH; is completely inhibited by 50% CO; and produces bilirubin IX-alpha, identified spectrophotometrically and chromatographically. Moreover, duodenal heme oxygenase was shown to release inorganic (55)Fe from (55)Fe-heme. Along the intestinal tract, enzyme activity was found to be highest in the duodenum where hemoglobin iron absorption is reported to be most active. Furthermore, when rats were made iron deficient, duodenal heme oxygenase activity and hemoglobin-iron absorption rose to a comparable extent. Upon iron repletion of iron-deficient animals, duodenal enzyme activity returned towards control values. In contrast to heme oxygenase, duodenal xanthine oxidase activity fell sharply in iron deficiency and rose towards base line upon iron repletion. Our findings suggest that mucosal heme oxygenase catalyzes the cleavage of heme absorbed in the intestinal mucosa and thus plays an important role in the absorption of hemoglobin iron. The mechanisms controlling this intestinal enzyme activity and the enzyme's role in the overall regulation of hemoglobin-iron absorption remain to be defined.
D000818:Animals; D001663:Bilirubin / Q000096:biosynthesis; D002855:Chromatography, Thin Layer; D004386:Duodenum / Q000201:enzymology; D006400:Hematocrit; D006418:Heme / Q000378:metabolism*; D006454:Hemoglobins / Q000378:metabolism*; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000201:enzymology* / Q000378:metabolism; D007501:Iron / Q000378:metabolism*; D000090463:Iron Deficiencies; D007504:Iron Radioisotopes; D008099:Liver / Q000201:enzymology; D008297:Male; D008861:Microsomes / Q000201:enzymology; D010105:Oxygenases / Q000378:metabolism*; D051381:Rats; D014969:Xanthine Oxidase / Q000378:metabolism
D006454:Hemoglobins; D007504:Iron Radioisotopes; D006418:Heme; D007501:Iron; D010105:Oxygenases; D014969:Xanthine Oxidase; D001663:Bilirubin