622 XIII. HEMOGLOBIN AND PORPHYRIN SYNTHES S 



a few hours and only small amounts of iron are absorbed. The experi- 

 ments of Austoni and Greenberg {100) with Fe^^ and those of Copp 

 and Greenberg {jkS9) with Fe^^ on normal and irondeficient rats 

 confirm the influence of the iron stores on the degree of iron absorp- 

 tion. The larger absorption of iron in anemic rats is due to the slower 

 passage through the intestines, which is probably due to the lowered 

 intestinal tone. Relatively more iron (30% of 0.05 mg.) was absorbed 

 by the nonanemic rats than by nonanemic dogs; this was increased 

 to over 90% in anemic rats {J^Sd). 



The mechanism of the absorption of iron through the intestinal 

 mucosa has been studied by Granick {1033) with interesting results. 

 The saturation of the mucosa with iron is accompanied by an accu- 

 mulation of ferritin which can be demonstrated by the observation of 

 ferritin crystals in the mucosa after immersion in 10% cadmium 

 sulfate. In normal growing guinea pigs ferritin can only be found in 

 traces in the duodenal region (c/. also 308) ; nor is there any evidence 

 for the presence of the iron-free apoferritin, which crystallizes as 

 readily as ferritin in cadmium sulfate. When 10 mg. iron is fed, there 

 is a marked increase of ferritin all along the gastrointestinal tract, 

 on continued feeding even in the stomach. An equilibrium: 



Intestine Mucosal cell Blood serum 



Fe3+ > Fe2+ ^ ^ Fe3+ 



it 

 Ferritin (Fe3+) 



is postulated. Only when the ferritin in the mucosa cell is lowered 

 by giving off iron to the blood can more iron be absorbed. Apparently 

 the formation of apoferritin in the mucosal cell is the limiting factor 

 of the rate of absorption. 



It is still uncertain to what degree the absorption of large doses of 

 iron given j>er os is subject to the same control. The use of high doses 

 of iron in hypochromic anemia has been reintroduced into medical 

 treatment by Lichtenstein {1731^) and Meulengracht {1923), and its 

 value is now generally recognized. Fowler and Barer {926) have, 

 however, pointed out the danger of iron cirrhosis of the liver which 

 may be incurred if large doses of iron are given over long periods. 



4.3. Incorporation of Iron in the Hemoglobin Molecule 



Experiments of Hahn, Whipple, and collaborators with radioactive 

 iron {1091 ,1092,109 Jf) fed to anemic dogs or man have shown that the 



