#4 NS 160 Cellular Nutrient Sensing

#4 NS 160 Cellular Nutrient Sensing - Cellular nutrient...

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Cellular nutrient Sensing III Part I: Regulation of Iron Homeostasis Part II: Nuclear Hormone Receptors
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IRON HOMEOSTASIS Nutritional control of sequence specific mRNA stability and translation Transition metal that can act as prothetic groups (such as heme) in a large number of enzymes and proteins. Ability to switch redox states (ferrous Fe ++ , ferric Fe +++ ) allows Fe to catalyze oxidation and reduction reactions but excessive Fe load promotes generation of reactive radicals that damage the cells and tissues. Fe uptake, distribution and export must be tightly regulated as iron deficiency can cause anemia while iron overload leads to heart and liver failure.
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Heme and nonheme iron from the diet is absorbed by the small intestine to replace iron loss from cell shedding and bleeding (there is no active excretion). The majority (~70%) of the body’s ~3-5 g of iron is utilized by erythroid cells. Iron from senescent erythrocytes is recycled through phagocytosis by macrophages. IRON HOMEOSTASIS Nutritional control of sequence specific mRNA stability and translation Whitney et al, Understanding normal and clinical nutrition, 6th edition
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The first step of (nonheme) iron absorption is reduction from ferric to ferrous Fe by the reductase duodenal cytochrome b followed by transport across the apical membrane via DMT1 (divalent metal transporter 1). Export of Fe 2+ to the portal circulation is mediated by the basolateral transporter ferroportin followed by re- oxidation to Fe 3+ by the plasma ferroxidase ceruloplasmin or its membrane-bound homologue hephaestin. Circulating Fe 3+ is bound by the plasma iron carrier transferrin, which delivers iron to erythroid bone marrow and other tissues. IRON HOMEOSTASIS Nutritional control of sequence specific mRNA stability and translation Pantopoulos, Ann. N.Y. Acad. Sci, 2004
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Iron loaded transferrin binds to the cell surface transferrin receptor and undergoes endocytosis. Iron release is accomplished by acidification of the endosome to pH ~5.5. Iron is transported out of the late endosome by DMT1 and utilized for the synthesis of iron containing proteins. Excess of intracellular iron is sequestered into ferritin, a shell like protein composed of 24 H and L subunits that can store up to 4500 Fe atoms. IRON HOMEOSTASIS Nutritional control of sequence specific mRNA stability and translation Pantopoulos, Ann. N.Y. Acad. Sci, 2004
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IRON HOMEOSTASIS Nutritional control of sequence specific mRNA stability and translation Most cells can control iron uptake and intracellular availability by reciprocally regulating the expression of TfR1 and ferritin (as well as some other proteins). Regulation occurs on the translational level. TfR and ferritin (both H and L
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#4 NS 160 Cellular Nutrient Sensing - Cellular nutrient...

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