NS 3410 1st Edition Lecture 4Outline of Last LectureI. Membrane JunctionsII. Ventral body cavity membranesIII. Passive Membrane TransportIV. Active TransportOutline of Current LectureI. Regulation of Iron in the bodyII. The Movement of Fe into the BodyIII. Block Iron UptakeIV. Receptor Mediated Endocytosis of IronCurrent LectureI. Regulation of Iron in the body- Fe in body is a closed system- no way to get rid of excess amount- Different cell types use slightly different proteins to move Fe in, through and out of the cell- Whole body Fe homeostasis is controlled by several hormones-Erythropoietin (kidney)-Hepcidin (liver)-Erythroferrone (bone)- Key cells that need to regulate Fe-Macrophage-Enterocyte-HepatocyteThese notes represent a detailed interpretation of the professor’s lecture. GradeBuddy is best used as a supplement to your own notes, not as a substitute.-Erythroid precursorsII. The Movement of Fe into the Body- In enterocyte (intestinal cell), Fe reduced to Fe2+ by ferric reductase- Fe imported into cell by transcellular protein DMT1- Once in the cell, Fe can be stored as ferritin if not needed- If Fe is not exported across basolateral membrane into bloodstream, the Fe will be trapped in cell and lost in feces- If Fe is needed, it is exported by ferroportin- Fe must be in Fe3+ form to bind to TfR-Fe2+ oxidized to Fe3+ by hephaestin- Fe3+ binds to specific serum protein, transferrin, to keep it bound and not in reactive state- Cells that express a receptor for transferrin can ingest this Fe by receptor mediated endocytosisIII. Block Iron Uptake- The primary role of regulation is the enterocyte, which needs to stop Fe from being absorbed or exported when there is already too much iron in the body- When there is excess of iron, liver makes hepcidin- Hepcidin is a hormone that binds to its receptor which is ferroportin-By doing this, the complex is internalized and degraded trapping Fe in the cellIV. Receptor Mediated Endocytosis of Iron- Cell senses that it needs iron- Transferrin receptors (TfR) expressed on outer cell membrane- Transferrin in circulation binds 2 atoms of iron- Fe-loaded transferrin binds to TfR on cell membrane- Complex is internalized into clathrin coated vesicle- Clathrin is unloaded from vesicle and returns to cell membrane- Endosome is acidified using proton pumps- Iron released from TfR-Tf complex at acidic pH- Iron is exported out of endosome by DMT1 to be used by cell- Apotransferrin- TfR complex is recycled back to cell membrane- Apotransferrin dissociates from