The Nematode Transcriptome Resource
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Hyperbilirubinemia
Porphyrins Porphyrins (Porphins) are cyclic tetrapyrol compounds formed by the linkage )). of four pyrrole rings through methenyl bridges (( HC In the reduced porphyrins (Porphyrinogens) the linkage of four pyrrole rings (tetrapyrol) through methylene bridges (( CH2 )) The characteristic property of porphyrins is the formation of complexes with the metal ion bound to nitrogen atoms of the pyrrole rings. e.g. Heme (iron porphyrin). Proteins which contain heme ((hemoproteins)) are widely distributed e.g. Hemoglobin, Myoglobin, Cytochromes, Catalase & Tryptophan pyrrolase. Natural porphyrins have substituent side chains on the eight hydrogen atoms numbered on the pyrrole rings. These side chains are: CH 1-Methyl-group (M)… (( 3 )) 2-Acetate-group (A)… (( CH2COOH )) 3-Propionate-group (P)… (( CH2CH2COOH )) 4-Vinyl-group (V)… (( CH CH2 )) Porphyrins with asymmetric arrangement of the side chains are classified as type III porphyrins while those with symmetric arrangement of the side chains are classified as type I porphyrins. Only types I & III are present in nature & type III series is more important because it includes heme. 1 Heme Biosynthesis Heme biosynthesis occurs through the following steps: 1-The starting reaction is the condensation between succinyl-CoA ((derived from citric acid cycle in the mitochondria)) & glycine, this reaction is a rate limiting reaction in the hepatic heme synthesis, it occurs in the mitochondria & is catalyzed by ALA synthase (Aminolevulinate synthase) enzyme in the presence of pyridoxal phosphate as a cofactor. The product of this reaction is α-amino-β-ketoadipate which is rapidly decarboxylated to form δ-aminolevulinate (ALA). 2-In the cytoplasm condensation reaction between two molecules of ALA is catalyzed by ALA dehydratase enzyme to form two molecules of water & one 2 molecule of porphobilinogen (PBG) which is a precursor of pyrrole. -
Porphyrins & Bile Pigments
Bio. 2. ASPU. Lectu.6. Prof. Dr. F. ALQuobaili Porphyrins & Bile Pigments • Biomedical Importance These topics are closely related, because heme is synthesized from porphyrins and iron, and the products of degradation of heme are the bile pigments and iron. Knowledge of the biochemistry of the porphyrins and of heme is basic to understanding the varied functions of hemoproteins in the body. The porphyrias are a group of diseases caused by abnormalities in the pathway of biosynthesis of the various porphyrins. A much more prevalent clinical condition is jaundice, due to elevation of bilirubin in the plasma, due to overproduction of bilirubin or to failure of its excretion and is seen in numerous diseases ranging from hemolytic anemias to viral hepatitis and to cancer of the pancreas. • Metalloporphyrins & Hemoproteins Are Important in Nature Porphyrins are cyclic compounds formed by the linkage of four pyrrole rings through methyne (==HC—) bridges. A characteristic property of the porphyrins is the formation of complexes with metal ions bound to the nitrogen atom of the pyrrole rings. Examples are the iron porphyrins such as heme of hemoglobin and the magnesium‐containing porphyrin chlorophyll, the photosynthetic pigment of plants. • Natural Porphyrins Have Substituent Side Chains on the Porphin Nucleus The porphyrins found in nature are compounds in which various side chains are substituted for the eight hydrogen atoms numbered in the porphyrin nucleus. As a simple means of showing these substitutions, Fischer proposed a shorthand formula in which the methyne bridges are omitted and a porphyrin with this type of asymmetric substitution is classified as a type III porphyrin. -
UROPORPHYRINOGEN HII COSYNTHETASE in HUMAN Hemolysates from Five Patientswith Congenital Erythropoietic Porphyriawas Much Lower
UROPORPHYRINOGEN HII COSYNTHETASE IN HUMAN CONGENITAL ERYTHROPOIETIC PORPHYRIA * BY GIOVANNI ROMEO AND EPHRAIM Y. LEVIN DEPARTMENT OF PEDIATRICS, THE JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE Communicated by William L. Straus, Jr., April 24, 1969 Abstract.-Activity of the enzyme uroporphyrinogen III cosynthetase in hemolysates from five patients with congenital erythropoietic porphyria was much lower than the activity in control samples. The low cosynthetase activity in patients was not due to the presence of a free inhibitor or some competing en- zymatic activity, because hemolysates from porphyric subjects did not interfere either with the cosynthetase activity of hemolysates from normal subjects or with cosynthetase prepared from hematopoietic mouse spleen. This partial deficiency of cosynthetase in congenital erythropoietic porphyria corresponds to that shown previously in the clinically similar erythropoietic porphyria of cattle and explains the overproduction of uroporphyrin I in the human disease. Erythropoietic porphyria is a rare congenital disorder of man and cattle, characterized by photosensitivity, erythrodontia, hemolytic anemia, and por- phyrinuria.1 Many of the clinical manifestations of the disease can be explained by the production in marrow, deposition in tissues, and excretion in the urine and feces, of large amounts of uroporphyrin I and coproporphyrin I, which are products of the spontaneous oxidation of uroporphyrinogen I and its decarboxyl- ated derivative, coproporphyrinogen I. In cattle, the condition is inherited -
Biochemistry I Enzymes
BIOCHEMISTRY I 3rd. Stage Lec. ENZYMES Biomedical Importance: Enzymes, which catalyze the biochemical reactions, are essential for life. They participate in the breakdown of nutrients to supply energy and chemical building blocks; the assembly of those building blocks into proteins, DNA, membranes, cells, and tissues; and the harnessing of energy to power cell motility, neural function, and muscle contraction. The vast majority of enzymes are proteins. Notable exceptions include ribosomal RNAs and a handful of RNA molecules imbued with endonuclease or nucleotide ligase activity known collectively as ribozymes. The ability to detect and to quantify the activity of specific enzymes in blood, other tissue fluids, or cell extracts provides information that complements the physician’s ability to diagnose and predict the prognosis of many diseases. Further medical applications include changes in the quantity or in the catalytic activity of key enzymes that can result from genetic defects, nutritional deficits, tissue damage, toxins, or infection by viral or bacterial pathogens (eg, Vibrio cholerae). Medical scientists address imbalances in enzyme activity by using pharmacologic agents to inhibit specific enzymes and are investigating gene therapy as a means to remedy deficits in enzyme level or function. In addition to serving as the catalysts for all metabolic processes, their impressive catalytic activity, substrate specificity, and stereospecificity enable enzymes to fulfill key roles in additional processes related to human health and well-being. Proteases and amylases augment the capacity of detergents to remove dirt and stains, and enzymes play important roles in producing or enhancing the nutrient value of food products for both humans and animals. -
Michael Koch Strukturanalyse Der Mitochondrialen
Michael Koch Strukturanalyse der mitochondrialen Protoporphyrinogen IX Oxidase aus Nicotiana tabacum und von zwei weiteren Proteinen: Blaues Cupredoxin Umecyanin aus Meerrettich (Armoracia rusticana) Lumazinsynthase-W27Y-Mutante aus Spalthefe (Schizosaccharomyces pombe) Technische Universität München Max-Planck-Institut für Biochemie Abteilung Strukturforschung Strukturanalyse der mitochondrialen Protoporphyrinogen IX Oxidase aus Nicotiana tabacum und von zwei weiteren Proteinen: Umecyanin und Lumazinsynthase-W27Y-Mutante Michael Koch Vollständiger Abdruck der von der Fakultät für Chemie der Technischen Universität München zur Erlangung des akademischen Grades eines Doktors der Naturwissenschaften (Dr. rer. nat.) genehmigten Dissertation. Vorsitzender: Univ.-Prof. Dr. W. Hiller Prüfer der Dissertation 1. apl. Prof. Dr. Dr. h. c. R. Huber 2. Univ.-Prof. Dr. Dr. A. Bacher Die Dissertation wurde am 24.02.2004 bei der Technischen Universität München eingereicht und durch die Fakultät für Chemie am 23.03.2004 angenommen. Dissertation Michael Koch Seite 3 Teile der Arbeit sind zur Veröffentlichung eingereicht bzw. wurden bereits veröffentlicht in: Koch, M., Breithaupt, C., Kiefersauer, R., Freigang, J., Huber, R., Messerschmidt, A. Crystal Structure of Protoporphyrinogen IX Oxidase: A key enzyme in heme and chlorophyll biosynthesis (EMBO J., online veröffentlicht 1. April 2004) Koch, M., Breithaupt, C., Kiefersauer, R., Freigang, J., Huber, R. and Messerschmidt, A. (2004). Crystal Structure of Protoporphyrinogen IX Oxidase. Jahrestagung der Deutschen Gesellschaft für Kristallographie 2004, Jena (Vortrag) Koch, M., Kiefersauer, R., Huber, R. (2002) Improvement of freezing protein crystals by accurately controlled humidity changes. Poster presentation at the XIX Congress and general assembly of the International Union of Crystallography, Geneva, Switzerland (Posterpräsentation) Koch, M., Velarde, M., Echt, S., Harrison, M., Dennison, C., Messerschmidt, A. -
Model Name: "Jamshidi2007
SBML Model Report Model name: “Jamshidi2007 - Genome-scale metabolic network of Mycobacterium tuberculosis (iNJ661)” 2LATEX July 28, 2015 1 General Overview This is a document in SBML Level 3 Version 1 format. Table1 shows an overview of the quantities of all components of this model. Table 1: Number of components in this model, which are described in the following sections. Element Quantity Element Quantity compartment types 0 compartments 2 species types 0 species 826 events 0 constraints 0 reactions 1025 function definitions 0 global parameters 19 unit definitions 1 rules 0 initial assignments 0 Model Notes Jamshidi2007 - Genome-scale metabolic networkof Mycobacterium tuberculosis (iNJ661) This model is described in the article:Investigating the metabolic capabilities of Mycobac- terium tuberculosis H37Rv using the in silico strain iNJ661 and proposing alternative drug tar- gets.Jamshidi N, Palsson B.BMC Syst Biol 2007; 1: 26 Abstract: Produced by SBML2LATEX 1 BACKGROUND: Mycobacterium tuberculosis continues to be a major pathogen in the third world, killing almost 2 million people a year by the most recent estimates. Even in industrialized countries, the emergence of multi-drug resistant (MDR) strains of tuberculosis hails the need to develop additional medications for treatment. Many of the drugs used for treatment of tuber- culosis target metabolic enzymes. Genome-scale models can be used for analysis, discovery, and as hypothesis generating tools, which will hopefully assist the rational drug development process. These models need to be able to assimilate data from large datasets and analyze them. RESULTS: We completed a bottom up reconstruction of the metabolic network of Mycobac- terium tuberculosis H37Rv. -
Significance of Heme and Heme Degradation in the Pathogenesis Of
International Journal of Molecular Sciences Review Significance of Heme and Heme Degradation in the Pathogenesis of Acute Lung and Inflammatory Disorders Stefan W. Ryter Proterris, Inc., Boston, MA 02118, USA; [email protected] Abstract: The heme molecule serves as an essential prosthetic group for oxygen transport and storage proteins, as well for cellular metabolic enzyme activities, including those involved in mitochondrial respiration, xenobiotic metabolism, and antioxidant responses. Dysfunction in both heme synthesis and degradation pathways can promote human disease. Heme is a pro-oxidant via iron catalysis that can induce cytotoxicity and injury to the vascular endothelium. Additionally, heme can modulate inflammatory and immune system functions. Thus, the synthesis, utilization and turnover of heme are by necessity tightly regulated. The microsomal heme oxygenase (HO) system degrades heme to carbon monoxide (CO), iron, and biliverdin-IXα, that latter which is converted to bilirubin-IXα by biliverdin reductase. Heme degradation by heme oxygenase-1 (HO-1) is linked to cytoprotection via heme removal, as well as by activity-dependent end-product generation (i.e., bile pigments and CO), and other potential mechanisms. Therapeutic strategies targeting the heme/HO-1 pathway, including therapeutic modulation of heme levels, elevation (or inhibition) of HO-1 protein and activity, and application of CO donor compounds or gas show potential in inflammatory conditions including sepsis and pulmonary diseases. Keywords: acute lung injury; carbon monoxide; heme; heme oxygenase; inflammation; lung dis- ease; sepsis Citation: Ryter, S.W. Significance of Heme and Heme Degradation in the Pathogenesis of Acute Lung and Inflammatory Disorders. Int. J. Mol. 1. Introduction Sci. -
Conversion of Amino Acids to Specialized Products
Conversion of Amino Acids to Specialized Products First Lecture Second lecture Fourth Lecture Third Lecture Structure of porphyrins Porphyrins are cyclic compounds that readily bind metal ions (metalloporphyrins)—usually Fe2+ or Fe3+. Porphyrins vary in the nature of the side chains that are attached to each of the four pyrrole rings. - - Uroporphyrin contains acetate (–CH2–COO )and propionate (–CH2–CH2–COO ) side chains; Coproporphyrin contains methyl (–CH3) and propionate groups; Protoporphyrin IX (and heme) contains vinyl (–CH=CH2), methyl, and propionate groups Structure of Porphyrins Distribution of side chains: The side chains of porphyrins can be ordered around the tetrapyrrole nucleus in four different ways, designated by Roman numerals I to IV. Only Type III porphyrins, which contain an asymmetric substitution on ring D are physiologically important in humans. Physiologically important In humans Heme methyl vinyl 1) Four Pyrrole rings linked together with methenyle bridges; 2) Three types of side chains are attached to the rings; arrangement of these side chains determines the activity; 3) Asymmetric molecule 3) Porphyrins bind metal ions to form metalloporphyrins. propionyl Heme is a prosthetic group for hemoglobin, myoglobin, the cytochromes, catalase and trptophan pyrrolase Biosynthesis of Heme The major sites of heme biosynthesis are the liver, which synthesizes a number of heme proteins (particularly cytochrome P450), and the erythrocyte-producing cells of the bone marrow, which are active in hemoglobin synthesis. Heme synthesis occurs in all cells due to the requirement for heme as a prosthetic group on enzymes and electron transport chain. The initial reaction and the last three steps in the formation of porphyrins occur in mitochondria, whereas the intermediate steps of the biosynthetic pathway occur in the cytosol. -
NEMBASE4: the Nematode Transcriptome Resource
Edinburgh Research Explorer NEMBASE4: the nematode transcriptome resource Citation for published version: Elsworth, B, Wasmuth, J & Blaxter, M 2011, 'NEMBASE4: the nematode transcriptome resource', International Journal For Parasitology, vol. 41, no. 8, pp. 881-94. https://doi.org/10.1016/j.ijpara.2011.03.009 Digital Object Identifier (DOI): 10.1016/j.ijpara.2011.03.009 Link: Link to publication record in Edinburgh Research Explorer Document Version: Publisher's PDF, also known as Version of record Published In: International Journal For Parasitology General rights Copyright for the publications made accessible via the Edinburgh Research Explorer is retained by the author(s) and / or other copyright owners and it is a condition of accessing these publications that users recognise and abide by the legal requirements associated with these rights. Take down policy The University of Edinburgh has made every reasonable effort to ensure that Edinburgh Research Explorer content complies with UK legislation. If you believe that the public display of this file breaches copyright please contact [email protected] providing details, and we will remove access to the work immediately and investigate your claim. Download date: 05. Oct. 2021 International Journal for Parasitology 41 (2011) 881–894 Contents lists available at ScienceDirect International Journal for Parasitology journal homepage: www.elsevier.com/locate/ijpara NEMBASE4: The nematode transcriptome resource ⇑ Benjamin Elsworth a, James Wasmuth b, Mark Blaxter a, a Institute of Evolutionary Biology, The University of Edinburgh, EH9 3JT, UK b Department of Comparative Biology and Experimental Medicine, Faculty of Veterinary Medicine, 3330, Hospital Drive, University of Calgary, Calgary, Alberta, Canada T2N 4N1 article info abstract Article history: Nematode parasites are of major importance in human health and agriculture, and free-living species Received 21 December 2010 deliver essential ecosystem services. -
Erythrocyte Uroporphyrinogen I Synthase Activity As an Indicator of Acute Porphyria
ANNALS OF CLINICAL AND LABORATORY SCIENCE, Vol. 19, No. 2 Copyright © 1989, Institute for Clinical Science, Inc. Erythrocyte Uroporphyrinogen I Synthase Activity as an Indicator of Acute Porphyria DONALD T. FORMAN, Ph .D. Division of Laboratory Medicine, Department o f Pathology, University o f North Carolina, Chapel Hill, NC 27514 ABSTRACT The pre-clinical diagnosis of acute intermittent porphyria (AIP) is important because acute attacks can be brought about by drugs, liver toxins, hormonal changes and diet. There also may be no obvious precipi tating agent. The discovery that the activity of uroporphyrinogen I syn thase (URO-S) activity in the red blood cells of patients with AIP is half that found in normal persons is of great value in diagnosing this disorder and also appears useful in detecting patients with the latent disease who have normal urinary delta-aminolevulinic acid and porphobilinogen excre tion. It also appears to distinguish other types of porphyria from acute intermittent porphyria. It must also be recognized that some red blood cells URO-S determinations will yield indeterminate results; therefore, repeat assays, including examination of kinship, will improve discrimina tion and confidence in the final diagnosis. Introduction porphyria is the most common form of porphyria, with an incidence of one in Acute intermittent porphyria (AIP) is 1 0 0 ,0 0 0 , occurring more often in women frequently familial and is inherited as an than in men. The age of onset is usually autosomal dominant trait with variable after puberty, suggesting a steroid-linked penetrance, therefore the variability of or hormonal initiated pathobiological symptoms. -
Case Report Treatment of Congenital Erythropoietic Porphyria in Children by Allogeneic Stem Cell Transplantation: a Case Report and Review of the Literature
Bone Marrow Transplantation (2001) 27, 101–105 2001 Nature Publishing Group All rights reserved 0268–3369/01 $15.00 www.nature.com/bmt Case report Treatment of congenital erythropoietic porphyria in children by allogeneic stem cell transplantation: a case report and review of the literature PH Shaw1, AJ Mancini1, JP McConnell2, D Brown1 and M Kletzel1 Departments of 1Pediatrics and Dermatology, Northwestern University Medical School and Children’s Memorial Hospital, Chicago, IL; and 2Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA Summary: ocular complications, hemolytic anemia and extreme photo- sensitivity which results in mutilating scarring. The anemia Congenital erythropoietic porphyria (CEP) is a rare may be severe enough to require chronic transfusion. As a autosomal recessive disorder of porphyrin metabolism result of the ravages of this disease, people who have it in which the genetic defect is the deficiency of uropor- historically have a shorter life expectancy. phyrinogen III cosynthase (UIIIC). Deficiency of this Many modalities have been used to treat this disease1–24 enzyme results in an accumulation of high amounts of with temporary, if any, effect because they are supportive uroporphyrin I in all tissues leading to hemolytic ane- and do not address the primary cause of the disease, the mia, splenomegaly, erythrodontia, bone fragility, deficiency of uroporphyrinogen III cosynthase. Thus far, exquisite photosensitivity and mutilating skin lesions. stem cell transplantation (SCT) is the only curative therapy We describe the case of a 23-month-old boy who was for CEP. It is effective because the transplanted stem cells cured of his CEP by a matched-sibling allogeneic bone produce normal levels of UIIIC and reverse the disease marrow transplant, and review the published clinical manifestations. -
Acute Intermittent Porphyria Antonio Dajer, MD; Louis Cooper, MD
CASE REPORT Acute Intermittent Porphyria Antonio Dajer, MD; Louis Cooper, MD A 34-year-old pregnant woman presented for evaluation of severe, persistent abdominal pain. Case A 34-year-old woman presented to the ED with severe, persistent abdomi- nal pain that had begun 18 days earlier. She was 7 weeks pregnant and had been seen in the same ED the day before. During that visit, ultra- sound had shown a single pregnancy of doubtful viability. Abdominal magnetic resonance imaging was normal. She was given multiple doses of hydromorphone. The discharge diagnosis was “missed abortion.” Since the onset of her pain, she had been hospitalized twice elsewhere, with no clear diagnosis to explain her pain. Treatment consisted of repeat doses of hydromorphone. During the second hospitalization, a sodium level of 109 mEq/L had been corrected with hypertonic saline, and a urinary tract infection (UTI) had been treated with cephalexin. Our patient had never experienced similar abdomi- nal pain. Her medical history included depression and asthma. Her family history was notable for an aunt who had died of lung cancer. On this ED visit, the patient’s vital signs were nor- mal. On examination, she was moaning in pain and clutching her abdomen. The abdomen was tender in both lower quadrants, with guarding but no re- bound. Her sodium level was 125 mEq/L; the day before it had been 132 mEq/L. Urine dipstick testing showed 2+ glucose and 2+ bilirubin; both had been within normal range (negative) the day before. An abdominal/pelvic computed tomography scan with intravenous (IV) and oral contrast did not reveal any potential cause of the patient’s pain.