China
Africa
Explore chapters and articles related to this topic
Liver Diseases
Published in George Feuer, Felix A. de la Iglesia, Molecular Biochemistry of Human Disease, 2020
George Feuer, Felix A. de la Iglesia
The pathway of heme formation has been demonstrated a long time ago.414,510,511 All nitrogen atoms and eight carbon atoms of the heme molecule are derived from glycine, the remaining carbon atoms derive from succinate via the Krebs’ cycle. In the first step, glycine and succinate are combined, and two of the resulting δ-aminolevulinic acid molecules are condensed to give monopyrrole porphobilinogen. The next step is an enzymatic polymerization of four porphobilinogen units leading to the formation of uroporphyrinogen. Subsequently, decarboxylation yields coproporphyrinogen; a side chain modification transforms this compound to protoporphyrinogen IX and finally, the incorporation of ferrous ion gives rise to heme and the addition of a globin leads to hemoglobin459 (Figure 8). The heme molecule is the prostetic group of a variety of hemoproteins such as hemoglobin, myoglobin, cytochromes, catalase, peroxidase, and others.
Sideroblastic Anemia and Porphyrias
Published in Harold R. Schumacher, William A. Rock, Sanford A. Stass, Handbook of Hematologic Pathology, 2019
Uroporphyrinogen III is converted to coproporphyrinogen III by an enzymatic reaction catalyzed by uroporphyrinogen decarboxylase. From its site of synthesis in the cytoplasm, coproporphyrinogen III reenters the mitochrondria and, in an enzyme reaction catalyzed by coproporphyrinogen oxidase, is converted to protoporphyrinogen IX. In a reaction catalyzed by protoporphyrinogen oxidase, protoporphyrinogen IX is oxidized to protoporphyrin IX. Finally, heme is produced by a reaction catalyzed by ferrochetalase or heme synthetase, in which a ferrous iron atom is inserted in the center of the protoporphyrin IX ring.
Wood’s lamp
Published in Dimitris Rigopoulos, Alexander C. Katoulis, Hyperpigmentation, 2017
Juliano Peruzzo, Clarissa Prieto Herman Reinehr, Tania Cestari
Based on the fact that delta-aminolevulinic acid (ALA)–derived porphyrins accumulate in neoplastic tissues, the use of ALA has been used to diagnose premalignant and malignant conditions. It also helps in the distinguishing of tumor from healthy tissue and benign lesions.19 ALA ointment (20%) was applied to the tumor and left on for 4–6 hours under occlusion, allowing protoporphyrinogen IX (PpIX) to accumulate; after the time interval, the area is illuminated with WL,20 showing a PpIX area in intense orange-red, which strongly contrasts with the green fluorescence of the normal biological tissues.19 WL has been proven to be very useful in the diagnosis of basal cell epithelioma, squamous cell epithelioma, Bowen’s disease, solar keratosis, and extramammary Paget’s disease.17,20 Additionally, it also provided a better delineation of the lesion margins.19
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
MDS and myeloproliferative syndromes (MPN) associated with ring sideroblasts are defined by the World Health Organization as MDS with RS and single lineage dysplasia (MDS-RS-SLD); MDS with RS and multilineage dysplasia (MDS-RS-MLD); and MDS/MPN with RS and thrombocytosis (MDS/MPN-RS-T) [160]. Between 65% and 85% of MDS/MPN with RS are associated with acquired SF3B1 mutations [161–163]. SF3B1 (splicing factor 3B subunit 1) is a key protein of the spliceosome. SF3B1 mutations in MDS/MPN with RS are heterozygous and missense with allelic frequencies between 35% and 43% [161–163]. RNA-sequencing in SF3B1-mutated cells showed evidence of dysregulation of mRNA splicing because of misrecognition of 3’ splice sites, conducing to frameshifts [162,163]. Half of the aberrantly spliced mRNA are eliminated by the nonsense medicated mRNA decay (NMD) [164,165]. Among those, PPOX and ABCC7 mRNA are downregulated in SF3B1-mutated cells [164,166]. PPOX is the gene of protoporphyrinogen oxidase, which catalyzes the dehydrogenation of protoporphyrinogen IX to form protoporphyrin IX, an essential step for heme production. Germinal mutations in ABCC7 are responsible for congenital sideroblastic anemia with cerebellar ataxia [163,166]. ABCB7 is a mitochondrial ATP-cassette binding membrane transporter involved in the transfer of iron-sulfur (Fe-S) groups into the cytoplasm, which is required for assembling Fe-S cluster-containing proteins, such as hemoglobin [167]. Silencing ABCC7 induces accumulation of iron in the mitochondria of HeLa cells and human erythroid progenitors [168]. Upregulating ABCC7 expression by lentiviral transduction in CD34+ cells isolated from four patients with MDS-RS restored effective erythropoiesis and inhibited mitochondrial iron accumulation [169].