A decrease in the amount of heme within erythrocytes activates the heme-controlled inhibitor leading to phosphorylation of which factor?

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Quizplus · Accepted Answer

The heme-controlled inhibitor phosphorylates eIF-2, which is a key factor in the initiation of protein synthesis. This phosphorylation inhibits the initiation of translation, thereby reducing protein synthesis in response to low heme levels.  One mechanism by which initiation of translation in eukaryotes is affected is phosphorylation of a ser(S) residue in the α-subunit of eIF-2. Within reticulocytes the phosphorylation of eIF-2 is the result of an activity called heme-controlled inhibitor (HCI). When heme is limiting it would be a waste of energy for reticulocytes to make globin protein, since active hemoglobin could not be generated. Therefore, when the level of heme falls, HCI becomes activated, leading to the phosphorylation of eIF-2 and reduced globin synthesis. Removal of phosphate is catalyzed by a specific eIF-2 phosphatase which is unaffected by heme.

A Decrease in the Amount of Heme Within Erythrocytes Activates