Iron and the liver.
Iron is essential for life, but iron overload is toxic and potentially fatal. The liver is a major site of iron storage and is particularly susceptible to injury from iron overload, especially when (as in primary hemochromatosis) the iron accumulates in hepatocytes. Iron can be taken up by the liver in several forms and by several pathways including: (1) receptor-mediated endocytosis of diferric or monoferric transferrin or ferritin, (2) reduction and carrier-facilitated internalization of iron from transferrin without internalization of the protein moiety of transferrin, (3) electrogenic uptake of low molecular weight, non-protein bound forms of iron, and (4) uptake of heme from heme-albumin, heme-hemopexin, or hemoglobin-haptoglobin complexes. Normally, pathway 2 is probably the major one for uptake of iron by hepatocytes. Iron is stored in the liver in the cores of ferritin shells and as hemosiderin, an insoluble product derived from iron-rich ferritin. Iron in hepatocytes stimulates translation of ferritin mRNA and represses transcription of DNA for transferrin and transferrin receptors. The major pathologic effects of chronic hepatic iron overload are: (1) fibrosis and cirrhosis, (2) porphyria cutanea tarda, and (3) hepatocellular carcinoma. Although precise pathogenetic mechanisms remain unknown, iron probably produces these and other toxic effects by increasing oxidative stress and lysosomal lability. Vigorous efforts at diagnosis and treatment of iron overload are essential since the pathologic effects of iron are totally preventable by early vigorous iron removal and prevention of iron re-accumulation.
Bonkovsky
H L
HL
Department of Medicine, University of Massachusetts Medical Center, Worcester 01655.
D001205:Ascorbic Acid / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000378:metabolism; D003094:Collagen / Q000378:metabolism; D005609:Free Radicals; D006432:Hemochromatosis / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007501:Iron / Q000378:metabolism* / Q000633:toxicity; D008099:Liver / Q000378:metabolism*; D008103:Liver Cirrhosis / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000378:metabolism; D008247:Lysosomes / Q000502:physiology; D008564:Membrane Potentials; D011164:Porphyrias / Q000503:physiopathology*; D011188:Potassium / Q000494:pharmacology; D014168:Transferrin / Q000378:metabolism; D014578:Uroporphyrins / Q000378:metabolism; D014810:Vitamin E / Q000378:metabolism
D005609:Free Radicals; D014168:Transferrin; D014578:Uroporphyrins; D014810:Vitamin E; D003094:Collagen; D007501:Iron; D001205:Ascorbic Acid; D011188:Potassium