Reticulocytes control the rate of globin synthesis as a consequence of the level of heme in the cell. This prevents globin protein from being made when there are insufficient amounts of heme. Which of the following best explains the effects of heme on protein synthesis in these cells?
A) a heme-controlled phosphatase dephosphorylates cap-binding factor, which prevents recognition of globin mRNA by the ribosomes
B) a tRNA degrading enzyme is active in the absence of heme
C) heme normally activates peptidyltransferase in reticulocytes
D) RNA polymerase activity is decreased in reticulocytes by low heme
E) the initiation factor eIF-2 becomes phosphorylated, reducing its level of activity

Question

Quizplus · Accepted Answer

Heme regulates protein synthesis by affecting the phosphorylation state of the initiation factor eIF-2. In the absence of heme, eIF-2 becomes phosphorylated, which reduces its activity and thus decreases protein synthesis. One mechanism by which initiation of translation in eukaryotes is effected is phosphorylation of a ser(S) residue in the α-subunit of eIF-2. The factor eIF-2 requires activation by interaction with GTP. The energy of GTP hydrolysis is used during translational initiation, thereby allowing eIF-2 to have GDP bound instead of GTP. In order to reactivate eIF- 2, the GDP must be exchanged for GTP. This requires an additional protein of the GEF family known as eIF- 2B. The phosphorylated form of eIF-2, in the absence of the eIF-2B, is just as active an initiator of translation as the nonphosphorylated form. However, when eIF-2 is phosphorylated, the GDP-bound complex is stabilized and exchange for GTP is inhibited. When eIF-2 is phosphorylated it binds eIF-2B more tightly, thus slowing the rate of exchange. It is this inhibited exchange that affects the rate of initiation. Within reticulocytes the phosphorylation of eIF-2 is the result of an activity called heme-controlled inhibitor (HCI). When the level of heme falls, HCI becomes activated, leading to the phosphorylation of eIF-2 and reduced globin synthesis.

Reticulocytes Control the Rate of Globin Synthesis as a Consequence