tailieunhanh - ANEMIAS AND OTHER RED CELL DISORDERS - PART 7

giản thể sinh tổng hợp heme. Heme sinh tổng hợp bắt đầu trong ty thể với sự ngưng tụ của succinyl-CoA và glycine tạo thành axit 5-aminolevulinic (δ-aminolevulinic acid). Sinh tổng hợp di chuyển vào bào tương của nhiều bước enzyme sản xuất coproporphyrinogen III. Phân tử này đi vào ty thể cho các bước cuối cùng của quá trình sinh tổng hợp heme. | 222 STEM CELL DYSFUNCTION SECTION IV FIGURE 12-2 Simplified schema of heme biosynthesis. Heme biosynthesis begins in the mitochondrion with the condensation of succinyl-CoA and glycine to form 5-aminolevulinic acid 8-aminolevulinic acid . Biosynthesis moves to the cytosol where multiple enzymatic stepsproduce coproporphyrinogen III. This molecule enters the mitochondrion for the final steps of heme biosynthesis. sideroblasts abnormal erythroblasts with excessive mitochondrial iron deposition in the bone marrow is the phenotypic expression of a heterogeneous group of disorders whose unifying feature is deranged heme biosynthesis. Unraveling of the biochemistry and genetics of sideroblastic anemia provides unique insight into heme and iron metabolism along with an expanded understanding of erythropoiesis. Center stage in this drama features the heme molecule. Figure 12-2 is a simplified schema of heme biosynthesis. The process begins in the mitochondrion with the condensation of glycine and succinyl-CoA to form 8-aminolevulinic acid ALA with pyridoxal phosphate as a The processing of ALA then moves to the cytoplasm where serial enzymatic transformations produce coproporphyrinogen III. This molecule enters the mitochondrion where additional modifications including the insertion of iron into the protoporphyrin IX ring by ferrochelatase produce heme. Numerous studies involving various subtypes of sideroblastic anemias demonstrate impaired heme Most commonly the sideroblastic anemias are classified as hereditary or acquired conditions Table 12-6 . The hereditary forms are primarily X-linked although some families display autosomal dominant or autosomal CHAPTER 12 I THE MYELODYSPLASTIC SYNDROMES 223 TABLE 12-6 CATEGORIES OF SIDEROBLASTIC ANEMIA Category Groups Etiology Hereditary X-linked Autosomal dominant Autosomal recessive Mitochondrial cytopathy Wolfram syndrome ALAS-2 mutations hABC7 gene Unknown Unknown mtDNA deletions Mutations in WFS1