PathwayStep404 PathwayStep403 eIF2 activation Formation of eIF2:GDP:eIF2B intermediate Recycling of eIF2:GDP Pubmed7063012 Reactome Database ID Release 4372731 Reactome, http://www.reactome.org ReactomeREACT_1815 The active eIF2:GTP complex may be formed by direct binding of GTP to free eIF2 or by GDP-GTP exchange on the eIF2:GDP:eIF2B complex. The eIF2:GDP complex binds eIF2B forming an eIF2:GDP:eIF2B intermediate complex. eIF2B is a guanine nucleotide releasing factor required to cause GDP release so that a new GTP molecule can bind and activate eIF2. Phosphorylated eIF2:GDP sequesters all eIF2B as an inactive complex, and thus, reuse of eIF2 is inhibited as a consequence of the tight bond it forms with eIF2B, which prevents nucleotide exchange. Therefore, in the absence of free eIF2B, excess eIF2 remains in its inactive GDP-bound form and protein synthesis slows dramatically.