China
Africa
Explore chapters and articles related to this topic
Orthomolecular Parenteral Nutrition Therapy
Published in Aruna Bakhru, Nutrition and Integrative Medicine, 2018
Arturo O'Byrne-Navia, Arturo O'Byrne-De Valdenebro
Pyridoxal 5-phosphate aids in the synthesis of hemoglobin, by serving as a coenzyme for the enzyme 5-aminolevulinic acid synthase (ALA-S), ALA-S is the first enzyme involved in the biosynthesis of the group heme (Erskine et al. 2003, Ajioka et al. 2006). For an enhanced binding of the oxygen to hemoglobin, PLP binds to two sites of this protein.
Molecular Mechanisms of Training Effects
Published in Atko Viru, Adaptation in Sports Training, 2017
It has been suggested that the key role in the increased activity of mitochondrial enzymes belongs to the induction of δ-aminolevulinic acid synthase by exercise.145 The effect of thyroxine is analogous. The activity of this enzyme in the red portion of the vastus lateralis muscle was doubled 17 h after a 4000-m run in rats. A similar change was obtained 14 h after injections of thyroxine. Before that, no change in heme-containing cytochrome c concentration occurred.148 δ-Aminolevulinic acid synthase is a rate-limiting enzyme in heme synthesis. This observation thus implies that up-regulation of heme synthesis is an early regulatory event mediated by muscle contraction and leading to an improvement of respiratory capacity.18
Consequences of an incomplete differential diagnosis
Published in James W. Albers, Stanley Berent, Neurobehavioral Toxicology: Neurological and Neuropsychological Perspectives, 2005
James W. Albers, Stanley Berent
Attacks of porphyria may be precipitated by many factors, the most important being medications (Meyer et al., 1972). The association of drug-induced porphyria has been known for a long time. The strongest precipitators are the barbiturates, although many other medications are implicated. Any drug metabolized by the hepatic cytochrome P-450 system is at risk for precipitating attacks. The barbiturates are known to amplify cytochrome P-450 synthesis as much as 40–50 times (Bissell, 1985; Sack, 1990). When the cytochrome P-450 system is activated, the intracellular heme reserve is incorporated into these hepatic cytochromes. As the heme concentration decreases, aminolevulinic acid synthase is disinhibited, and the porphyrin metabolic pathway is activated. Among patients with porphyria, the pathway is partially blocked, producing accumulation of porphyrin precursors and inhibition of heme synthesis necessary to replace the depleted stores.
A deep dive into future therapies for microcytic anemias and clinical considerations
Published in Expert Review of Hematology, 2023
François Rodrigues, Tereza Coman, Guillemette Fouquet, Francine Côté, Geneviève Courtois, Thiago Trovati Maciel, Olivier Hermine
Heme synthesis requires three substrates: succinyl-CoA, iron, and glycine. For each heme molecule synthesized, one atom of iron and eight molecules of glycine are needed [65]. It has been shown that reduced delivery of iron to erythroblasts reduces the synthesis of heme. Indeed, as written earlier, the mRNA of aminolevulinic acid synthase 2 (ALAS2), the first-step enzyme of heme production in red blood cells, is regulated by IRPs. In iron-deficiency, IRPs associate with the 5’ UTR IRE region of ALAS2 mRNA to inhibit its translation [15]. Reduced intracellular heme content then activates the heme regulated eIF2alpha kinase (HRI), which represses the translation of globin by phosphorylating the translation initiation factor eIF2 alpha [66]. Decreased heme and globin production thus leads to hypochromic and microcytic anemia in iron deficiency states. Interestingly, the development of microcytic anemia seems necessary for the survival of red blood cells during iron deficiency, as in iron depleted HRI(-/-) mice, globins devoid of heme aggregate within the erythroid lineage, resulting in a hyperchromic, normocytic anemia with decreased RBC counts, compensatory erythroid hyperplasia and accelerated apoptosis in the bone marrow and spleen [67].
Porphyria: awareness is the key to diagnosis!
Published in Acta Clinica Belgica, 2022
Benjamin Heymans, Wouter Meersseman
There are actually two forms of protoporphyria: erythropoietic protoporphyria (EPP) and X-linked protoporphyria (XLP). The molecular basis of EPP is a reduction (up) to less than 30% of the enzyme catalyzing the last step in the haem biosynthesis, ferrochelatase. EPP is an autosomal recessive disease, caused in the majority of cases by a combination of full inactivation of one allele and a faulty splicing of the mRNA of the other allele, further reducing the expression of the enzyme. In a minority of cases, a mutation in both alleles is present [13]. By contrast, in XLP with X-linked inheritance there is a gain-of-function mutation in delta-aminolevulinic acid synthase 2. This results in an overproduction of protoporphyrin. Part of this excess is transformed by ferrochelatase to zinc-bound protoporphyrin.
Expression profile analysis reveals hub genes that are associated with immune system dysregulation in primary myelofibrosis
Published in Hematology, 2021
Haotian Ma, Jincen Liu, Zilong Li, Huaye Xiong, Yulei Zhang, Yanping Song, Jianghua Lai
5-Aminolevulinic acid synthase (ALAS) is encoded by ALAS2 and can catalyze the formation of 5-aminolevulinic acid from succinyl-coenzyme A and glycine, which is the first step in haemoglobin synthesis [50]. Increased haemoglobin synthesis could promote haematopoietic cell differentiation [51]. The upregulated expression of ALAS2 could cause enhanced haem production, haemoglobinization, and erythropoiesis [52]. In this study, we found that the expression of ALAS2 was enhanced in patients, reflecting that ALAS2, similar to EPB42 and SLC4A1, could affect the abnormally increased erythropoiesis in PMF [53], which may be related to ineffective erythropoiesis. Ineffective erythropoiesis is one of the main causes of anaemia and organomegaly. In addition, several studies revealed that haem- or haemoglobin-related genes were also expressed in non-erythrocyte cells, such as cervicovaginal epithelial cells and murine macrophages, in response to different stress conditions [54,55]. It is well established that haem is an important molecular factor for cellular physiological and metabolic functions. However, excessive free haem has toxic effects on cells [56]. In this study, we conjecture that the enhanced expression of ALAS2 reflects an increased level of haem, indicating a feasible reason for the immunological response in patients with PMF.