Multiple mechanisms for hereditary sideroblastic anemia.

Kazumichi Furuyama; Shigeru Sassa

Home/Archive/PubMed

PubMed · 11929048

Multiple mechanisms for hereditary sideroblastic anemia.

Kazumichi Furuyama·Shigeru Sassa

View original source ↗Export metadata ↓

Abstract

Hereditary sideroblastic anemia (HSA) is a heterogeneous group of inherited anemic disorders which is characterized by the presence of ringed sideroblasts in the bone marrow, microcytic hypochromic anemia and typically its X-linked inheritance in patients. It has been shown that a deficiency of the erythroid-specific delta-aminolevulinate synthase (ALAS-E) activity is responsible for pyridoxine-responsive HSA in many patients, however, the pathogenesis of other types of HSA remains still unknown. In this article, recent evidence suggesting multiple causes for HSA is summarized and discussed.

Explore related subjects

5-Aminolevulinate Synthetase Anemia, Sideroblastic Family Health Genetic Heterogeneity Humans Point Mutation Protein Binding Succinate-CoA Ligases Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.Review

Keep this discovery

Explore connections, maps & timelines

BibTeX RIS

Kazumichi Furuyama, Shigeru Sassa. 2002. Multiple mechanisms for hereditary sideroblastic anemia.. https://pubmed.ncbi.nlm.nih.gov/11929048/

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2006

Decrease of hepatic delta-aminolevulinate dehydratase activity in an animal model of fatigue.

Fatigue can be defined physiologically as inability to maintain the expected power output. At present, no standard of fatigue are yet available. In order to find biomarkers of fatigue, we investigated the level of delta-aminolevulinic acid (ALA), the first intermediate metabolite in the heme biosynthetic pathway, in the plasma and urine of an animal model of fatigue. To prepare fatigued animals, we kept rats for 5 days in a cage filled with water to a height of 1.5 cm. As a result, the plasma and urinary ALA levels were increased in the fatigued animals as compared with those in the control animals. One day after the rats had been returned to their normal cages, these increased levels were restored to the control ones. We also examined the activity of the enzyme ALA dehydratase (ALAD), which is the second enzyme in the heme biosynthetic pathway, and ALAD gene expression during the fatigue and its recovery sessions. The ALAD activity, as well as its gene expression, in the liver of the fatigued animals was decreased as compared with those of the control animals. Both activity and gene expression of ALAD were recovered to their respective control levels after the rats had been allowed to rest in their normal cages for 1 day. Furthermore, the activity of ALA synthase (ALAS), the rate-limiting enzyme in the heme biosynthesis, in the liver was increased after the fatigue session for 5 days. Although this level of increase in the plasma concentration of ALA may not induce fatigue, increase in plasma and urinary ALA levels can be biomarkers of fatigue.

5-Aminolevulinate Synthetase↗

PubMed2006

Mechanism and substrate stereochemistry of 2-amino-3-oxobutyrate CoA ligase: implications for 5-aminolevulinate synthase and related enzymes.

The condensation process catalysed by 2-amino-3-oxobutyrate CoA ligase (KBL; also known as 2-amino-3-ketobutyrate ligase) involves the loss of the pro-R hydrogen atom of glycine and occurs with the inversion of stereochemistry; a similar scenario is envisaged for the condensation step of other alpha-oxoamine synthases.

5-Aminolevulinate Synthetase↗

PubMed2006

Histone acetyltransferase p300 regulates the transcription of human erythroid-specific 5-aminolevulinate synthase gene.

Erythroid-specific 5-aminolevulinate synthase (ALAS2) catalyzes the rate-limiting step in heme biosynthesis of erythroid cells. Here, we show that treatment of erythroid K562 cells with HDAC inhibitors sodium butyrate or Trichostatin A gave rise to a significant increase in ALAS2 gene transcripts, with a concurrent increase in acetylation level of histone H4 at the ALAS2 gene promoter. Histone acetyltransferase p300 bound withALAS2 promoter and overexpression of p300 increased both the promoter reporter expression and endogenous mRNA level of ALAS2. Additionally, two functional Sp1 sites located in ALAS2 promoter were identified. Both of the GATA-1 sites and all the Sp1 sites at the ALAS2 promoter contributed to the transcription synergistic action with p300. These data implicated a close relationship between the acetylation modification of histone at the ALAS2 promoter and the regulation of this gene. Meanwhile, this work identified that ALAS2 is a novel target gene for p300/CBP action as histone acetyltransferases.

5-Aminolevulinate Synthetase↗