Hemoglobin synthesis by erythrocytes continues throughout a vertebrate's lifetime. The mechanism of mammalian heme synthesis has been studied for many years; aminolevulinate synthase 2 (ALAS2), a heme synthetase, is associated with X-linked dominant protoporphyria in humans. Amphibian and mammalian blood cells differ, but little is known about amphibian embryonic hemoglobin synthesis. We investigated the function of the Xenopus alas2 gene (Xalas2) in primitive amphibian erythrocytes and found that it is first expressed in primitive erythroid cells before hemoglobin alpha 3 subunit (hba3) during primary hematopoiesis and in the posterior ventral blood islands at the tailbud stage. Xalas2 is not expressed during secondary hematopoiesis in the dorsal lateral plate. Hemoglobin was barely detectable by o-dianisidine staining and hba3 transcript levels decreased in Xalas2-knockdown embryos. These results suggest that Xalas2 might be able to synthesize hemoglobin during hematopoiesis and mediate erythrocyte differentiation by regulating hba3 expression in Xenopus laevis.
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http://dx.doi.org/10.1016/j.bbrc.2014.11.110 | DOI Listing |
J Agric Food Chem
January 2025
Key Laboratory of Industrial Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi, Jiangsu 214122, China.
5-Aminolevulinic acid synthase (ALAS) is the key rate-limiting enzyme in the synthesis of the vital biosynthetic intermediate 5-aminolevulinic acid (ALA). However, its catalytic efficiency is compromised due to its low activity and poor stability. Here, we obtained the mutant I325M/V390Y/H391I (T6), which exhibited a 7.
View Article and Find Full Text PDFScience
December 2024
Developmental Biology Program, Sloan Kettering Institute, New York, NY, USA.
microRNAs (miRNAs) and small interfering RNAs (siRNAs) are 21- to 22-nucleotide RNAs that guide Argonaute-class effectors to targets for repression. In this work, we uncover 5-aminolevulinic acid synthase 1 (ALAS1), the initiating enzyme for heme biosynthesis, as a general repressor of miRNA accumulation. Although heme is known to be a positive cofactor for the nuclear miRNA processing machinery, ALAS1-but not other heme biosynthesis enzymes-limits the assembly and activity of Argonaute complexes under heme-replete conditions.
View Article and Find Full Text PDFBiochemistry
January 2025
Department of Chemistry, University of Florida, 126 Sisler Hall, Gainesville, Florida 32611, United States.
5-Aminolevulinate synthase (ALAS) is a PLP-dependent enzyme that catalyzes the production of 5-aminolevulinate from succinyl-CoA and glycine. Its ability to catalyze the essentially irreversible - bond formation has significant potential in chemoenzymatic synthesis of α-amino ketones. Native ALAS, unfortunately, is extremely substrate-selective, and this seriously limits its synthetic utility.
View Article and Find Full Text PDFBlood
January 2025
Department of Pediatrics, Hematology, The Children's Hospital of Philadelphia, Philadelphia, PA.
X-linked sideroblastic anemia (XLSA) is a congenital anemia caused by mutations in ALAS2, a gene responsible for heme synthesis. Treatments are limited to pyridoxine supplements and blood transfusions, offering no definitive cure except for allogeneic hematopoietic stem cell transplantation, only accessible to a subset of patients. The absence of a suitable animal model has hindered the development of gene therapy research for this disease.
View Article and Find Full Text PDFHematology Am Soc Hematol Educ Program
December 2024
Harvard Medical School, Boston, MA.
The acute hepatic porphyrias (AHPs) are a family of rare genetic diseases associated with attacks of abdominal pain, vomiting, weakness, neuropathy, and other neurovisceral symptoms. Pathogenic variants in 1 of 4 enzymes of heme synthesis are necessary for the development of AHP, and the onset of acute attacks also requires the induction of δ-aminolevulinic acid synthase 1 (ALAS1), the first and rate-limiting step of heme synthesis in the liver. Givosiran is an RNA interference medication that inhibits hepatic ALAS1 and was designed to treat AHP.
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