The heme level regulates the globin synthesis because _____.

Expert Solution

Heme regulates protein synthesis during erythroid differentiation

Protein synthesis in erythroid progenitors is mainly dependent on heme level that is sensed by HRI, a member of a family of protein kinases able to phosphorylate the ?-subunit of the eukaryotic translation initiation factor (eIF2?). Once phosphorylated, eIF2? causes the inhibition of protein synthesis.41 HRI is predominantly expressed in the erythroid compartment61 and its kinase activity is directly regulated by heme level. Heme binding to the kinase domain of HRI inhibits its activity leading to decreased eIF2? phosphorylation and increased rate of translation, mainly of ?- and ?-globin mRNAs. On the other hand, during heme deficiency, the activation of HRI and subsequent phosphorylation of eIF2? cause the inhibition of protein synthesis. Thus, only following the initiation of heme biosynthesis in differentiating erythroid progenitors, the inhibition of HRI activity allows the synthesis of ?- and ?-globins. In this manner, HRI is fundamental to ensure that no globin is synthesized in excess of what can be assembled into hemoglobin

queen_honey_blossom answered 1 year ago

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