R411C mutation of the ALAS2 gene encodes a pyridoxine-responsive enzyme with low activity |
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| Authors: | Kazumichi Furuyama,Ritsuko Uno,Akio Urabe,Norio Hayashi,Hiroyoshi Fujita,Masao Kondo,Shigeru Sassa,& Masayuki Yamamoto |
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| Affiliation: | Department of Biochemistry, Tohoku University School of Medicine, Sendai, Japan; The Rockefeller University, New York, U.S.A.; Inagi City Hospital, Tokyo, Japan; Kanto Teishin Hospital, Tokyo, Japan; Molecular Biology, Tohoku University School of Medicine, Sendai, Japan; The Institute of Public Health, Tokyo, Japan; Centre of Tsukuba Advanced Research Alliance and Institute of Basic Medical Science, University of Tsukuba, Tsukuba, Japan |
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| Abstract: | A R411C missense mutation of the erythroid-specific δ-aminolaevulinate synthase (ALAS2) gene was identified in a pedigree with X-linked pyridoxine-responsive sideroblastic anaemia (XLSA). The normal and the mutant cDNAs were expressed in E. coli , and the enzyme protein was purified. ALAS activity of the mutant enzyme was 12% and 25%, when incubated in the absence and the presence of pyridoxal 5'-phosphate, respectively, compared with that of the wild-type enzyme. These findings suggest that the R411C mutation accounts for low ALAS activity and a partial pyridoxine-responsiveness of the disease in the patient. |
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| Keywords: | δ-aminolaevulinate synthase (E.C.2.3.1.37), ALAS2 sideroblastic anaemia pyridoxine |
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