ArticleThe Journal of biological chemistry2012
X-linked sideroblastic anemia due to carboxyl-terminal ALAS2 mutations that cause loss of binding to the β-subunit of succinyl-CoA synthetase (SUCLA2).
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 53 citations in OpenAlex.
- Heme as a versatile signaling molecule: Coordinating mitochondrial metabolism with global cellular responses.The Journal of biological chemistry · 2026Review
- BMSC-derived exosomal ANTXR1 inhibits erythroid differentiation by suppressing the TLR4/MyD88/NF-κB signaling pathway.Scientific reports · 2026Article
- Elucidating the Role of Human ALAS2 C-terminal Mutations Resulting in Loss of Function and Disease.Biochemistry · 2024Article
- Case report: A novel 11-bp deletion in exon 11 causing a frameshift in the C-terminal of theFrontiers in medicine · 2024Article
- The yeast ALA synthase C-terminus positively controls enzyme structure and function.Protein science : a publication of the Protein Society · 2023Article
- Proteomic Analysis of Ferrochelatase Interactome in Erythroid and Non-Erythroid Cells.Life (Basel, Switzerland) · 2023Article
- Iron Metabolism in the Disorders of Heme Biosynthesis.Metabolites · 2022Review
- Cutting-Edge Therapies and Novel Strategies for Acute Intermittent Porphyria: Step-by-Step towards the Solution.Biomedicines · 2022Review
- Regulation of Heme Synthesis by Mitochondrial Homeostasis Proteins.Frontiers in cell and developmental biology · 2022Review
- An Extended C-Terminus, the Possible Culprit for Differential Regulation of 5-Aminolevulinate Synthase Isoforms.Frontiers in molecular biosciences · 2022Review
- Ferrochelatase: Mapping the Intersection of Iron and Porphyrin Metabolism in the Mitochondria.Frontiers in cell and developmental biology · 2022Review
- The immunometabolite itaconate inhibits heme synthesis and remodels cellular metabolism in erythroid precursors.Blood advances · 2021Article
- Dosage Compensation in Females with X-Linked Metabolic Disorders.International journal of molecular sciences · 2021Review
- Tartryl-CoA inhibits succinyl-CoA synthetase.Acta crystallographica. Section F, Structural biology communications · 2020Article
- Human aminolevulinate synthase structure reveals a eukaryotic-specific autoinhibitory loop regulating substrate binding and product release.Nature communications · 2020Article
- Hereditary Ataxia: A Focus on Heme Metabolism and Fe-S Cluster Biogenesis.International journal of molecular sciences · 2020Review
- Molecular expression, characterization and mechanism of ALAS2 gain-of-function mutants.Molecular medicine (Cambridge, Mass.) · 2019Article
- Glutamine via α-ketoglutarate dehydrogenase provides succinyl-CoA for heme synthesis during erythropoiesis.Blood · 2018Article
- Structure of the Mitochondrial Aminolevulinic Acid Synthase, a Key Heme Biosynthetic Enzyme.Structure (London, England : 1993) · 2018Article
- Iron metabolism in erythroid cells and patients with congenital sideroblastic anemia.International journal of hematology · 2018Review
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Authors and funding
5 authors at 3 institutions in 3 countries.
Funding
Abstract
Mutations in the erythroid-specific aminolevulinic acid synthase gene (ALAS2) cause X-linked sideroblastic anemia (XLSA) by reducing mitochondrial enzymatic activity. Surprisingly, a patient with the classic XLSA phenotype had a novel exon 11 mutation encoding a recombinant enzyme (p.Met567Val) with normal activity, kinetics, and stability. Similarly, both an expressed adjacent XLSA mutation, p.Ser568Gly, and a mutation (p.Phe557Ter) lacking the 31 carboxyl-terminal residues also had normal or enhanced activity, kinetics, and stability. Because ALAS2 binds to the β subunit of succinyl-CoA synthetase (SUCLA2), the mutant proteins were tested for their ability to bind to this protein. Wild type ALAS2 bound strongly to a SUCLA2 affinity column, but the adjacent XLSA mutant enzymes and the truncated mutant did not bind. In contrast, vitamin B6-responsive XLSA mutations p.Arg452Cys and p.Arg452His, with normal in vitro enzyme activity and stability, did not interfere with binding to SUCLA2 but instead had loss of positive cooperativity for succinyl-CoA binding, an increased K(m) for succinyl-CoA, and reduced vitamin B6 affinity. Consistent with the association of SUCLA2 binding with in vivo ALAS2 activity, the p.Met567GlufsX2 mutant protein that causes X-linked protoporphyria bound strongly to SUCLA2, highlighting the probable role of an ALAS2-succinyl-CoA synthetase complex in the regulation of erythroid heme biosynthesis.
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