GENETICS AND DEVELOPMENT OF ERYTHROID HEME ENZYMES
Principal Investigator: S Sassa
Abstract: DESCRIPTION: (Adapted from investigator's abstract) Heme synthesis is regulated in a highly tissue-specific manner. In particular, erythroid heme synthesis is regulated either by the erythroid-specific isozymes, or by upregulation of the erythroid-specific delta-aminolevulinate (ALA) synthase (ALAS2) by heme, the end-product of the heme biosynthetic pathway, while hepatic heme synthesis is downregulated by heme at the level of the non-specific delta-aminolevulinate (ALA) synthase (ALAS1). The specific aim of this study is to define the nature of the erythroid- specific control of heme synthesis and the role of heme in gene expression in erythroid cells. The focus will be placed on the role of NF-E2, the erythroid transcription factor, on erythroid gene expression, and the erythroid heme pathway gene expression, especially that of ALAS2, on erythroid differentiation. The investigators plan to examine the regulation of NF-E2 activity in erythroid differentiation and the regulation of the human ALAS (hALAS2) gene expression. These studies will hopefully clarify the role of ALAS2 and transcription factors such as NF-E2 and Bach1 in erythroid differentiation, and shed light on the distinct aspects of erythroid heme synthesis.
Funding Period: 1983-08-01 - 2004-01-31
more information: NIH RePORT
- Arg452 substitution of the erythroid-specific 5-aminolaevulinate synthase, a hot spot mutation in X-linked sideroblastic anaemia, does not itself affect enzyme activityKazumichi Furuyama
Department of Molecular Biology and Applied Physiology, Tohoku University School of Medicine, Sendai, Miyagi ken, Japan
Eur J Haematol 76:33-41. 2006....
- delta-Aminolevulinate dehydratase (ALAD) porphyria: the first case in North America with two novel ALAD mutationsReiko Akagi
Department of Nutritional Science, Okayama Prefectural University, Soja, Japan
Mol Genet Metab 87:329-36. 2006..This case represents the molecular analysis of the ALAD gene defects in the first case of ADP identified in North America, who is a compound heterozygote for two novel ALAD gene defects...
- Dual gene defects involving delta-aminolaevulinate dehydratase and coproporphyrinogen oxidase in a porphyria patientReiko Akagi
Okayama Prefectural University, Japan
Br J Haematol 132:237-43. 2006..This patient thus represents the first case of porphyria where both CPO and ALAD deficiencies were demonstrated at the molecular level...