title: Molecular defects of erythroid 5-aminolevulinate synthase in X-linked sideroblastic anemia.
abstract: The erythroid-specific isozyme of 5-aminolevulinate synthase (ALAS2), the first and rate-limiting enzyme of heme biosynthesis, is expressed concomitantly with the differentiation and maturation of the erythroid cell in order to accommodate generation of the large amounts of heme required for hemoglobin production. During the past few years the ALAS2 gene and its transcript have been characterized and the amino acid sequence of the enzyme deduced. The human genetic disorder X-linked sideroblastic anemia, previously postulated to be caused by defects of ALAS, has now been analyzed at the molecular and tissue-specific level. A heterogeneous group of point mutations in the catalytic domain of the ALAS2 enzyme has been found to cause the disorder. Impaired activity of recombinant mutant ALAS2 enzymes has also been demonstrated. Characterization of molecular defects in individuals with X-linked sideroblastic anemia has provided improved diagnosis for at-risk family members.
authors.affiliation: Department of Medicine, University of Oklahoma College of Medicine, Oklahoma City 73104, USA.
authors.forename: S S
authors.initials: SS
authors.lastname: Bottomley
authors.forename: B K
authors.initials: BK
authors.lastname: May
authors.forename: T C
authors.initials: TC
authors.lastname: Cox
authors.forename: P D
authors.initials: PD
authors.lastname: Cotter
authors.forename: D F
authors.initials: DF
authors.lastname: Bishop
mesh_terms: D000624:5-Aminolevulinate Synthetase / Q000097:blood / Q000235:genetics*; D000595:Amino Acid Sequence; D000756:Anemia, Sideroblastic / Q000175:diagnosis / Q000201:enzymology* / Q000235:genetics*; D004912:Erythrocytes / Q000201:enzymology*; D004920:Erythropoiesis; D008040:Genetic Linkage; D006454:Hemoglobins / Q000096:biosynthesis; D006801:Humans; D007527:Isoenzymes / Q000097:blood / Q000235:genetics*; D008969:Molecular Sequence Data; D017354:Point Mutation; D011110:Polymorphism, Genetic; D014960:X Chromosome
chemical_list: D006454:Hemoglobins; D007527:Isoenzymes; D000624:5-Aminolevulinate Synthetase