Erythroid 5-aminolevulinate synthase and X-linked sideroblastic anemia

Heme is an essential prosthetic group in proteins involved in electron and oxygen transport. It can exert regulatory roles at the translational level of some eukaryotic mRNAs and at the transcriptional level of certain genes by controlling the DNA binding of some transcription factors. Impairment of heme biosynthesis is associated with sideroblastic anemia. In man, the first step of the heme biosynthetic pathway is catalyzed by 5-aminolevulinate synthase. The human gene encoding erythroid 5-aminolevulinate synthase has been localized on the X chromosome. Recently mutations on the gene, with concomitant reduced ALAS activity, have been associated with X-linked sideroblastic anemia. The recent biochemical and molecular biological advances on 5-aminolevulinate synthase are assessed in light of a more global interpretation of X-linked sideroblastic anemia and heme biosynthesis.