APM Welcome, APM North West Network Conference, Synergies Across Sectors
Iron regulation slideshow
1. Iron in the body Three gens: Three essential actors HFe2 HAMP Tmprss6
2. Iron in the body Hepcidin It is the key regulator of body iron content. It is the master regulator of enteric iron absorption. It is produced by the liver, and it determines how much iron is absorbed from the diet and released from storage sites in the body. When its synthesis is defective causes iron loading. When over-production, is defective iron release and iron absorption. It is encoded by HAMP ( Hepcidin Antimicrobial Peptide ) that provides instructions for the production of Hepcidin. However has two regulators to prevent excess and deficiency: HFe2 and Tmprss6 genes
3. Normal level Iron excess is regulated through a pathway involving HFe2 that stimulates expression of the Hepcidin encoding HAMP gene. Iron attenuation is countered through a pathway involving the Hepatocyte-specific plasma membrane protease matriptase-2 encoded by Tmprss6 , leading to suppression of HAMP expression. Iron in the body On average, the body absorbs about 10 percent of the iron obtained from the diet. Iron in the body
4. Iron in the body How do they do? HFe2 stimulates expression of the HAMP gene Tmprss6 leading to suppression of HAMP expression.
5. Iron in the body HFe2 The official name is “hemochromatosis”, disorder that causes the body to absorb too much iron from the diet. The HFE protein interacts with other proteins on the cell surface to detect the amount of iron in the body and regulates the production of hepcidin. The regulation of intestinal iron absorption is crucial to avoid toxicity. Disruption of this regulation is hereditary hemochromatosis leads to iron overload, cirrhosis, cardiomyopathy, arthritis and endocrine failure. HFe2 provides instructions for producing hepcidin that is located in the surface of cells, primarily liver and intestinal cells. There are more than twenty mutations in this gen that cause hemochromatosis. Tmprss6 When it detects iron deficiency, blocks HAMP transcription, permitting enhance dietary iron absorption. It is required to sense iron deficiency.