DOCSLIB.ORG

The Biochemical Consequences of Hypoxia

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
The Biochemical Consequences of Hypoxia J Clin Pathol: first published as 10.1136/jcp.s3-11.1.14 on 1 January 1977. Downloaded from J. clin. Path., 30, Suppl. (Roy. Coll. Path.), 11, 14-20 The biochemical consequences of hypoxia K. G. M. M. ALBERTI From the Department of Chemical Pathology and Human Metabolism, General Hospital, Southampton Unlike plants which can utilize the energy obtained and creatine phosphate which is impaired. The rest from the sun through photosynthesis man requires of this review will be concerned with the production to oxidize substrates in order to obtain energy. This of ATP aerobically and anaerobically, examining energy is required for the many energy-utilizing or first glycolysis, then the tricarboxylic acid cycle, exergonic reactions which take place in the body and and finally the cytochrome system. The biochemical are necessary to sustain life (table I). Energy exists in consequences of hypoxia to the whole organism will then be discussed using two models in particular: Syntheses exercise where oxygen delivery remains normal but Active transport Muscular contraction tissue requirement greatly exceeds delivery and Nerve function hypoxia in relation to the whole organ. The final section will deal with possible methods of assessing Table I Energy-utilizing (exergonic) reactions tissue hypoxia in clinical situations. the body in several forms. First there is potential energy contained in macromolecules and second Glycolysis there is a group of compounds which have been copyright. termed high-energy phosphates which act as the The three parts of the carbohydrate oxidation system energy currency ofthe body. Thephrase 'high energy' take place in three different parts of the cell. is used because the free energy of hydrolysis of the Glycolysis is a cytoplasmic process: the tricarboxylic terminal phosphate is - 7000 cal/mol compared acid cycle is localized within the matrix of the mito- with - 4000 cal/mol for ordinary ester phosphates. chondrion while the electron transport chain occupies The major high energy phosphates are shown in the inner mitochondrial membrane. Glycolysis table II. These include ATP and the other nucleo- itself thus functions primarily as a preliminary step in the breakdown of glucose, although it should be http://jcp.bmj.com/ Nucleotides Others remembered that it also has important functions as a Adenosine triphosphate (ATP) Creatine phosphate means of converting an acute energy source, glucose, Guanosine triphosphate (GTP) I ,3-diphosphoglycerate (I ,3-DPG) into a storage form of energy, triglyceride, Compared Inosine triphosphate (ITP) Phosphoenolpyruvate (PEP) Cytidine triphosphate (CTP) with the tricarboxylic acid cycle the energy yield of Uridine triphosphate (UTP) glycolysis is small but it does have one unique Table II High-energy phosphates function. This is the ability to produce ATP anaerobically. on September 25, 2021 by guest. Protected tide phosphates. ATP in particular is ubiquitous The major energy-utilizing and producing steps and is involved in exergonic reactions through- of glycolysis are shown in the figure. It can be seen out the body. Its energy is used, for example, in that a high-energy phosphate is used up in admitting muscular contraction, in nervous excitation, for glucose to the pathway. A further ATP molecule is active transport and in the synthesis of compounds required to phosphorylate fructose-6-phosphate to such as fatty acids. Other high-energy phosphates fructose-1 ,6-diphosphate. Thereafter, however, energy with more limited roles also exist (table II). These is produced rather than used. ATP is produced include creatine phosphate whose role is restricted at two stages: the breakdown of 1,3-diphosphogly- purely to muscle, and 1,3-diphosphoglycerate and cerate and of phosphenolpyruvate. As two of each phosphenolpyruvate which are parts of the glycolytic of these molecules is made from one glucose molecule pathway. It should be remembered that other four ATP molecules will be produced per passage of biologically important compounds also fall into the one glucose molecule down the pathway. This gives high energy class. These include acetyl CoA, certain a net yield of two ATPs between glucose and amino acid esters, S-adenosyl methionine and pyruvate. This is equivalent to 15 000 cal/mol of uridine diphosphate glucose. glucose and in many senses is trivial in that it In hypoxia it is the synthesis particularly of ATP represents just over 2 per cent of the total potential 14 J Clin Pathol: first published as 10.1136/jcp.s3-11.1.14 on 1 January 1977. Downloaded from The biochemical consequences ofhypoxia 15 Glycoqen If all reactions in the shuttle were at equilibrium the pyridine nucleotides would equilibrate between Glucose _tGlucose - b- phosphate ATP ADP 4 cytoplasm and mitochondria. This would be un- Fructose- 6 - phosphate favourable in that a high cytosolic NAD is required jATP to drive glyceraldehyde 3-phosphate dehydrogenase ADP in the direction of glycolysis while in the mitochon- Fructose -1,6- diphosphate dria a high NADH is required to drive the electron Dihydroxy- acetone phosphate transport chain. This state is achieved by making one (2) Glyceraldehyde-3-phosphate of the reactions of the malate shuttle irreversible. NAD (2) This is either malate transport into the mitochondria (NADH (2) or aspartate transport out (Newsholme and Start, (2) 1,3-Diphosphoglycerate 1973). In hypoxia the transport system will rapidly HADP (2) break down. NADH will accumulate within the mitochondrion. Malate and NAD will rapidly (2) 3 - Phosphoqlycerate accumulate and malate will no longer get in. As a (2) Lactate result cytosolic malate and NADH will accumulate (2) NAD and the reaction sequence will cease. (2) NADH4'Jj Obviously glycolysis would cease entirely ifNADH (2) Pyruvate.e Phosphoenolpyruvate (2) accumulated in an uncontrolled way in the cyto- ATP(2) ADP(2) plasm in that no NAD would remain for glyceralde- Fig Energy-utilizing andproducing reactions of hyde 3-phosphate dehydrogenase. If this were the glycolysis. case even the anaerobic formation of ATP would cease and cells would die. The NAD is in fact restored by the reduction of pyruvate with NADH energy of glucose (686 000 cal/mol). This amount of yielding lactate and NAD. Thus an anaerobiosis energy is, however, sufficient to sustain certain lactate will accumulate in large amounts and will copyright. cells in the resting state when hypoxia or anoxia is spill out of the hypoxic cells into the circulation to be present. re-used when oxygen is again available. It can be seen that NADH is also produced during Regulation of glycolysis occurs at one main step: glycolysis. This represents a form of potential energy the conversion of fructose-6-phosphate to fructose and if fully oxidized will yield six further ATPs per 1,6-diphosphate. The enzyme, phosphofructokinase, mole of glucose. For this to occur, the NADH must is inhibited by ATP and citrate as well as by hydrogen first enter the mitochondrion. Mitochondria are, ions. Inhibition by ATP and citrate means that when http://jcp.bmj.com/ however, impermeable to NADH and a rather energy is plentiful and the tricarboxylic acid cycle roundabout route is followed, termed the 'malate- is saturated glycolysis will cease so that substrate oxaloacetate shuttle' (equations 1-4). First of all the is not passed unnecessarily down the glycolytic reducing equivalent of NADH is transferred to pathway. The inhibition by hydrogen ion is interest- oxaloacetate yielding malate. ing in that this will limit lactic acid production during (1) IN CYTOPLASM: exercise and will prevent intracellular pH dropping Oxaloacetate + NADH-vMALATE + NAD+ to unacceptably low levels. In hypoxia glycolysis is on September 25, 2021 by guest. Protected Malate then traverses the mitochondrial membrane accelerated due to the stimulation of phosphofructo- and is oxidized back to oxaloacetate restoring kinase by AMP and lack of ATP (Newsholme and NADH: Start, 1973). (2) IN MITOCHONDRION MALATE + NAD+ -vOxaloacetate + NADH Tricarboxylic acid cycle The oxaloacetate is then converted to aspartate. (3) IN MITOCHONDRION This forms the final common pathway for all oxida- Oxaloacetate + glutamate -*aspartate + 2- tive energy-yielding reactions. The glycolytic end oxoglutarate product pyruvate enters the cycle as acetyl CoA by Both aspartate and 2-oxoglutarate diffuse out of condensing with oxaloacetate. During the passage of the mitochondrion. the acetyl CoA round the cycle two CO2molecules are (4) IN CYTOPLASM generated so that there is no net gain of carbon 2-Oxoglutarate + aspartate -) oxaloacetate + compounds. There are, however, several steps at glutamate which energy is unleashed, generally in the form of The net result therefore is the translocation of NADH. These energy yielding steps are shown in NADH from the cytoplasm to the mitochondrion. equations 5-10. J Clin Pathol: first published as 10.1136/jcp.s3-11.1.14 on 1 January 1977. Downloaded from 16 K. G. M. M. Alberti (5) Pyruvic acid + NAD+ + CoA.SH-*acetyl CoA + NADH + H+ (6) Isocitric acid + NAD -+ ADP ATP ADP ATP Oxalosuccinic acid + NADH + H+ (11) NAD(H) < 4 flavoprotein - CoQ -p cytochromne b cytochime It (7) 2-Oxoglutaric acid + NAD+ + CoA.SH--÷ (ubiquinone) l Succinyl CoA.SH (8) Succinyl CoA + GDP -+ succinic acid + 02: cytochrome a3 cytochromc a - cytohrome c GTP + CoA.SH (cytochrome oxidase) ATP ADP (9) Succinic acid + FAD -+ Fumaric acid + FADH2 It is known that three ATP molecules are formed (10) Malic acid + NAD+ -+oxaloacetic acid from the free energy released during passage of the + NADH + H+ electron. It has been calculated that there must be a Each NADH formed will yield three ATP mole- free energy change of approximately 9000 calories cules. There is also one ATP equivalent formed in between two components of the chain if an ATP reaction 8 in the shape of GTP and the FADH2 molecule is to be formed at that point. Four sites produced in reaction 9 will yield two ATP molecules. fulfil these requirements and in fact three are used as There will thus be 15 ATP molecules formed from shown in equation 11.
Load more

Recommended publications
  • A Disease Spectrum for ITPA Variation: Advances in Biochemical and Clinical Research Nicholas E
    Burgis Journal of Biomedical Science (2016) 23:73 DOI 10.1186/s12929-016-0291-y REVIEW Open Access A disease spectrum for ITPA variation: advances in biochemical and clinical research Nicholas E. Burgis Abstract Human ITPase (encoded by the ITPA gene) is a protective enzyme which acts to exclude noncanonical (deoxy) nucleoside triphosphates ((d)NTPs) such as (deoxy)inosine 5′-triphosphate ((d)ITP), from (d)NTP pools. Until the last few years, the importance of ITPase in human health and disease has been enigmatic. In 2009, an article was published demonstrating that ITPase deficiency in mice is lethal. All homozygous null offspring died before weaning as a result of cardiomyopathy due to a defect in the maintenance of quality ATP pools. More recently, a whole exome sequencing project revealed that very rare, severe human ITPA mutation results in early infantile encephalopathy and death. It has been estimated that nearly one third of the human population has an ITPA status which is associated with decreased ITPase activity. ITPA status has been linked to altered outcomes for patients undergoing thiopurine or ribavirin therapy. Thiopurine therapy can be toxic for patients with ITPA polymorphism, however, ITPA polymorphism is associated with improved outcomes for patients undergoing ribavirin treatment. ITPA polymorphism has also been linked to early-onset tuberculosis susceptibility. These data suggest a spectrum of ITPA-related disease exists in human populations. Potentially, ITPA status may affect a large number of patient outcomes, suggesting that modulation of ITPase activity is an important emerging avenue for reducing the number of negative outcomes for ITPA-related disease.
    [Show full text]
  • Class 11 Biology Chapter- 13 Respiration in Plants
    CLASS 11 BIOLOGY CHAPTER- 13 RESPIRATION IN PLANTS CELLULAR RESPIRATION: The process of conversion of the chemical energy of organic substances into a metabolically usable energy within living cells is called cellular respiration. TYPES OF CELLULAR RESPIRATION: (i) Aerobic respiration: The process of respiration which requires molecular oxygen. (ii) Anaerobic respiration: The process of respiration which does not require molecular oxygen and occurs in the cytoplasm. MECHANISM OF RESPIRATION: Following are the steps- 1. GLYCOLYSIS / EMP Pathway: It involves a series of closely integrated reactions in which hexose sugars(usually glucose) are converted into pyruvic acid. It is common in both aerobic and anaerobic reactions. It occurs in the cytoplasm. It does not require oxygen. Gollowing are the steps of GLYCLOLYSIS: (i) Conversion of glucose to Fructose-1,6-diphosphate: First phosphorylation: Glucose is converted to Glucose -6-phosphate in the presence of enzyme hexokinase and Mg++ ions and energy in the form of ATP. Isomerization: Glucose-6-phosphate is converted to Fructose-6-phosphate in the presence of phosphohexoisomerase. Second phosphorylation: Fructose-6-phosphate is converted to Fructose-1,6- diphosphate by the use of energy in the form of ATP. (ii) Formation of pyruvic acid from fructose -1,6-diphosphate: Cleavage: Fructose-1,6-diphosphate splits into 3-phosphoglyceraldehyde and Dihydroxyacetone phosphate in the presence of enzyme aldolase. Phosphorylation and oxidative dehydrogenase: 3-phosphoglyceraldehyde is converted to 1,3-biphosphoglyceric acid. ATP generation(first): 1,3-biphosphoglyceric acid is converted to 3-phosphoglyceric acid in the presence of Mg++ and phosphoglycerokinase . Isomerization: 3-phosphoglyceric acid is converted to 2-phosphoglyceric acid in the presence of Mg++.
    [Show full text]
  • Inosine in Biology and Disease
    G C A T T A C G G C A T genes Review Inosine in Biology and Disease Sundaramoorthy Srinivasan 1, Adrian Gabriel Torres 1 and Lluís Ribas de Pouplana 1,2,* 1 Institute for Research in Biomedicine, Barcelona Institute of Science and Technology, 08028 Barcelona, Catalonia, Spain; [email protected] (S.S.); [email protected] (A.G.T.) 2 Catalan Institution for Research and Advanced Studies, 08010 Barcelona, Catalonia, Spain * Correspondence: [email protected]; Tel.: +34-934034868; Fax: +34-934034870 Abstract: The nucleoside inosine plays an important role in purine biosynthesis, gene translation, and modulation of the fate of RNAs. The editing of adenosine to inosine is a widespread post- transcriptional modification in transfer RNAs (tRNAs) and messenger RNAs (mRNAs). At the wobble position of tRNA anticodons, inosine profoundly modifies codon recognition, while in mRNA, inosines can modify the sequence of the translated polypeptide or modulate the stability, localization, and splicing of transcripts. Inosine is also found in non-coding and exogenous RNAs, where it plays key structural and functional roles. In addition, molecular inosine is an important secondary metabolite in purine metabolism that also acts as a molecular messenger in cell signaling pathways. Here, we review the functional roles of inosine in biology and their connections to human health. Keywords: inosine; deamination; adenosine deaminase acting on RNAs; RNA modification; translation Citation: Srinivasan, S.; Torres, A.G.; Ribas de Pouplana, L. Inosine in 1. Introduction Biology and Disease. Genes 2021, 12, 600. https://doi.org/10.3390/ Inosine was one of the first nucleobase modifications discovered in nucleic acids, genes12040600 having been identified in 1965 as a component of the first sequenced transfer RNA (tRNA), tRNAAla [1].
    [Show full text]
  • Standard Abbreviations
    Journal of CancerJCP Prevention Standard Abbreviations Journal of Cancer Prevention provides a list of standard abbreviations. Standard Abbreviations are defined as those that may be used without explanation (e.g., DNA). Abbreviations not on the Standard Abbreviations list should be spelled out at first mention in both the abstract and the text. Abbreviations should not be used in titles; however, running titles may carry abbreviations for brevity. ▌Abbreviations monophosphate ADP, dADP ‌adenosine diphosphate, deoxyadenosine IR infrared diphosphate ITP, dITP ‌inosine triphosphate, deoxyinosine AMP, dAMP ‌adenosine monophosphate, deoxyadenosine triphosphate monophosphate LOH loss of heterozygosity ANOVA analysis of variance MDR multiple drug resistance AP-1 activator protein-1 MHC major histocompatibility complex ATP, dATP ‌adenosine triphosphate, deoxyadenosine MRI magnetic resonance imaging trip hosphate mRNA messenger RNA bp base pair(s) MTS ‌3-(4,5-dimethylthiazol-2-yl)-5-(3- CDP, dCDP ‌cytidine diphosphate, deoxycytidine diphosphate carboxymethoxyphenyl)-2-(4-sulfophenyl)- CMP, dCMP ‌cytidine monophosphate, deoxycytidine mono- 2H-tetrazolium phosphate mTOR mammalian target of rapamycin CNBr cyanogen bromide MTT ‌3-(4,5-Dimethylthiazol-2-yl)-2,5- cDNA complementary DNA diphenyltetrazolium bromide CoA coenzyme A NAD, NADH ‌nicotinamide adenine dinucleotide, reduced COOH a functional group consisting of a carbonyl and nicotinamide adenine dinucleotide a hydroxyl, which has the formula –C(=O)OH, NADP, NADPH ‌nicotinamide adnine dinucleotide
    [Show full text]
  • Antibiotics As a Feed Additive Promote Growth of Chickens by Modulating the Gut Microbiome
    Antibiotics as a Feed Additive Promote Growth of Chickens by Modulating the Gut Microbiome Xiangkai Li ( [email protected] ) Lanzhou University https://orcid.org/0000-0002-5704-9791 Ying Wu Lanzhou University Liang Peng Lanzhou University Rong Han Lanzhou University pengya Feng Lanzhou University Aman Khan Lanzhou University Pu Liu Lanzhou University Research Keywords: Antibiotic, Gut microbiota, Metabonomic, Lipid and amid acid metabolism, Immune response Posted Date: June 7th, 2021 DOI: https://doi.org/10.21203/rs.3.rs-571302/v1 License: This work is licensed under a Creative Commons Attribution 4.0 International License. Read Full License Page 1/31 Abstract Background: Antibiotics widely used as growth promoters in the agricultural industry, but their mechanisms have not been fully explored. Antibiotics has a connection effect on the gut microbiome which plays a vital role in host metabolism and immune response. Here, we investigated the association of antibiotic and gut microbiome in broiler chicken. Methods: Polymyxin (PMX) and amoxicillin (AMX) were selected as feed additives in broiler chicken, and gut bacterial composition assessed by quantitative real-time PCR and high-throughput sequencing of bacterial 16S rRNA. Metabolome and lipidomic of feces and serum samples were analyzed using liquid chromatograpy-tandem mass spectrometry (LC-MS). We further assessed changes in the microbiota and metabolism which underwent antibiotics treatment. Results: The administration of antibiotic increasing, the average weight of chickens by up to 4.9% and altered number and structure of the intestinal microora compared to the un-treated group. The bacterial component of gut microbiota in antibiotic groups was showed a lower prevalence of Firmicutes and Bacteroidetes phyla and higher prevalence of a high diversity (Proteobacteria).
    [Show full text]
  • Epistasis-Driven Identification of SLC25A51 As a Regulator of Human
    ARTICLE https://doi.org/10.1038/s41467-020-19871-x OPEN Epistasis-driven identification of SLC25A51 as a regulator of human mitochondrial NAD import Enrico Girardi 1, Gennaro Agrimi 2, Ulrich Goldmann 1, Giuseppe Fiume1, Sabrina Lindinger1, Vitaly Sedlyarov1, Ismet Srndic1, Bettina Gürtl1, Benedikt Agerer 1, Felix Kartnig1, Pasquale Scarcia 2, Maria Antonietta Di Noia2, Eva Liñeiro1, Manuele Rebsamen1, Tabea Wiedmer 1, Andreas Bergthaler1, ✉ Luigi Palmieri2,3 & Giulio Superti-Furga 1,4 1234567890():,; About a thousand genes in the human genome encode for membrane transporters. Among these, several solute carrier proteins (SLCs), representing the largest group of transporters, are still orphan and lack functional characterization. We reasoned that assessing genetic interactions among SLCs may be an efficient way to obtain functional information allowing their deorphanization. Here we describe a network of strong genetic interactions indicating a contribution to mitochondrial respiration and redox metabolism for SLC25A51/MCART1, an uncharacterized member of the SLC25 family of transporters. Through a combination of metabolomics, genomics and genetics approaches, we demonstrate a role for SLC25A51 as enabler of mitochondrial import of NAD, showcasing the potential of genetic interaction- driven functional gene deorphanization. 1 CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria. 2 Laboratory of Biochemistry and Molecular Biology, Department of Biosciences, Biotechnologies and Biopharmaceutics,
    [Show full text]
  • Citric Acid Cycle
    Lecture: 4 Biochemistry Anwar J Almzaiel Citric acid cycle Citric acid cycle (Krebs cycle, tricarboxylic acid cycle) is a series of reactions in mitochondria that bring about the catabolism of acetyl residues, liberating hydrogen equivalents, which upon oxidation lead to the release of most the energy of tissues fuels. The major function of cycle is to act as the final common pathway for oxidation of fatty acids, carbohydrates and proteins. It includes the electron transport system, the energy is produced in large amounts. Several of these processes are carried out in many tissues but the liver is the only tissue in which all occur to a significant extent, thus it is lethal when large numbers of hepatic cell are damaged or replaced by connective tissue, as in acute hepatitis and cirrhosis respectively. This cycle is found in the mitochondria. It starts with pyruvic acid which comes from cytoplasm to the mitochondria to be converted with coenzymes (NAD) and enzymes into acetyl COA + Pyruvic acid + COA +NAD Acetyl CoA +NADH+ CO2 The enzymes needed are found in the mitochondria close to the enzymes of the respiratory chain The oxidation of pyruvate to acetyl-CoA Before pyruvate can enter the citric acid cycle, it must be transported into the mitochondria via a special pyruvate transporter that aids its passage across the inner mitochondrial membrane. Within the mitochondria, pyruvate is oxdatively decarboxylated into acetyl COA. The conversion of pyruvic acid to acetyl COA involves 5 types of reaction and each reaction is catalysed by different enzyme system these enzymes act as a multi enzyme system (complex).
    [Show full text]
  • High-Purity Rebaudioside D and Applications Hochreines Rebaudiosid-D Und Anwendungen Rébaudioside D De Grande Pureté Et Applications
    (19) TZZ Z_T (11) EP 2 708 548 B1 (12) EUROPEAN PATENT SPECIFICATION (45) Date of publication and mention (51) Int Cl.: of the grant of the patent: C07H 1/08 (2006.01) A21D 2/36 (2006.01) 06.12.2017 Bulletin 2017/49 A23G 1/42 (2006.01) (21) Application number: 13196410.8 (22) Date of filing: 13.10.2010 (54) High-Purity Rebaudioside D and Applications Hochreines Rebaudiosid-D und Anwendungen Rébaudioside D de grande pureté et applications (84) Designated Contracting States: (72) Inventors: AL AT BE BG CH CY CZ DE DK EE ES FI FR GB • Abelyan, Varuzhan GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO 50480 Kuala Lumpur (MY) PL PT RO RS SE SI SK SM TR • Markosyan, Avetik 59200 Kuala Lumpur (MY) (30) Priority: 15.10.2009 US 580233 • Abelyan, Lidia 24.05.2010 US 785501 50480 Kuala Lumpur (MY) 24.05.2010 US 785504 24.05.2010 US 785506 (74) Representative: Hocking, Adrian Niall et al 24.05.2010 US 785507 Albright IP Limited 24.05.2010 US 785508 County House 24.05.2010 US 786392 Bayshill Road 24.05.2010 US 786402 Cheltenham, Glos. GL50 3BA (GB) 24.05.2010 US 786413 24.05.2010 US 786416 (56) References cited: 24.05.2010 US 786427 WO-A1-2009/071277 24.05.2010 US 786430 24.05.2010 US 786419 • I. SAKAMOTO ET AL: "Application of 13C NMR spectroscopy to chemistry of natural glycosices: (43) Date of publication of application: rebaudioside-C,a newsweet diterpeneglycoside 19.03.2014 Bulletin 2014/12 of Stevia rebaudiana", CHEM.
    [Show full text]
  • Utilization of L-Methionine and S-Adenosyl-L-Methionine for Methylation of Soluble RNA by Mouse Liver and Hepatoma Extracts1
    [CANCER RESEARCH 27, 646-«S3,April 1967] Utilization of L-Methionine and S-Adenosyl-L-methionine for Methylation of Soluble RNA by Mouse Liver and Hepatoma Extracts1 R. L. HANCOCK The Jackson Laboratory, Bar Harbor, Maine SUMMARY following reaction: ATP + L-methionine = SAM + pyrophos The methyl group of L-methionine or S-adenosyl-L-methionine phate + monophosphate (7). SAM is used in the methylation of sRNA by sRNA methylases in the following reaction: sRNA + is used by nonparticulate mouse liver and hepatoma prepara SAM = methylated sRNA + S-adenosyl-L-homocysteine (10). tions to methylate soluble ribonucleic acid (sRNA). Esclierichia The two enzyme reactions are presented along with a representa coli K12 sRNA was a more active substrate than yeast sRNA. tion of the origin of the unmethylated sRNA (tp-RNA) in Chart Four different lots of E. coli B sRNA gave similar incorporations between lots. "Stripped" and "nonstripped" sRNA had similar 1. An array of RNA methylases exhibiting specificity for par ticular bases and for sRNA from different biologic sources, along amounts of methyl incorporation. Other nucleoside triphosphates with other, less si^ecific RNA methylases, has been described besides adenosine triphosphate were capable of sup]x>rting the incorjioration of methyl groups from L-methionine into sRNA. (11, 15, 16, 17, 22). The most extensively methylated sRNA molecules known have been found in mammary adenocarcinoma The nonspecificity of the nucleoside triphosphate reaction was tissue (3), and recently Mittelman et al. (18) have found RNA shown to be due to an adenosine diphosphokinase reaction and methylase activity to be extremely high in certain viral-induced not to nucleoside tri phosphate: L-methionine nucleosidyl trans- tumor cells.
    [Show full text]
  • Role of Inosine Triphosphate Pyrophosphatase Gene Variant on Fever Incidence During Zidovudine Antiretroviral Therapy
    Role of inosine triphosphate pyrophosphatase gene variant on fever incidence during zidovudine antiretroviral therapy A.V.C. Coelho1, S.P.S. Silva2, L. Zandonà3, G. Stocco3, G. Decorti3 and S. Crovella1,4 1Departamento de Genética, Universidade Federal de Pernambuco Federal de Pernambuco, Recife, PE, Brasil 2Programa de Pós-Graduação em Inovação Terapêutica, Universidade Federal de Pernambuco Federal de Pernambuco, Recife, PE, Brasil 3Department of Life Sciences, University of Trieste, Trieste, Italy 4Institute for Maternal and Child Health, Scientific Institute for Research, Hospitalization and Care Burlo Garofolo, Trieste, Italy Corresponding author: A.V.C. Coelho E-mail: [email protected] / [email protected] Genet. Mol. Res. 16 (1): gmr16019373 Received September 22, 2016 Accepted November 18, 2016 Published January 23, 2017 DOI http://dx.doi.org/10.4238/gmr16019373 Copyright © 2017 The Authors. This is an open-access article distributed under the terms of the Creative Commons Attribution ShareAlike (CC BY-SA) 4.0 License. ABSTRACT. Zidovudine, the antiretroviral drug used to treat HIV infection, commonly causes adverse effects, such as systemic fever and gastrointestinal alterations. In the present study, the potential role of inosine triphosphate pyrophosphatase (ITPA) gene variant on the incidence of adverse events during antiretroviral therapy (ART) of HIV with zidovudine was discussed. Individuals from Northeastern Brazil (N = 204) receiving treatment for HIV-1 infection were recruited. Zidovudine-related adverse effects developed during the treatment were registered. The rs1127354 polymorphism in the ITPA gene was Genetics and Molecular Research 16 (1): gmr16019373 A.V.C. Coelho et al. 2 genotyped using real-time PCR to assess whether this single nucleotide polymorphism was associated with the occurrence of zidovudine- related adverse effects.
    [Show full text]
  • The Metabolic Building Blocks of a Minimal Cell Supplementary
    The metabolic building blocks of a minimal cell Mariana Reyes-Prieto, Rosario Gil, Mercè Llabrés, Pere Palmer and Andrés Moya Supplementary material. Table S1. List of enzymes and reactions modified from Gabaldon et. al. (2007). n.i.: non identified. E.C. Name Reaction Gil et. al. 2004 Glass et. al. 2006 number 2.7.1.69 phosphotransferase system glc + pep → g6p + pyr PTS MG041, 069, 429 5.3.1.9 glucose-6-phosphate isomerase g6p ↔ f6p PGI MG111 2.7.1.11 6-phosphofructokinase f6p + atp → fbp + adp PFK MG215 4.1.2.13 fructose-1,6-bisphosphate aldolase fbp ↔ gdp + dhp FBA MG023 5.3.1.1 triose-phosphate isomerase gdp ↔ dhp TPI MG431 glyceraldehyde-3-phosphate gdp + nad + p ↔ bpg + 1.2.1.12 GAP MG301 dehydrogenase nadh 2.7.2.3 phosphoglycerate kinase bpg + adp ↔ 3pg + atp PGK MG300 5.4.2.1 phosphoglycerate mutase 3pg ↔ 2pg GPM MG430 4.2.1.11 enolase 2pg ↔ pep ENO MG407 2.7.1.40 pyruvate kinase pep + adp → pyr + atp PYK MG216 1.1.1.27 lactate dehydrogenase pyr + nadh ↔ lac + nad LDH MG460 1.1.1.94 sn-glycerol-3-phosphate dehydrogenase dhp + nadh → g3p + nad GPS n.i. 2.3.1.15 sn-glycerol-3-phosphate acyltransferase g3p + pal → mag PLSb n.i. 2.3.1.51 1-acyl-sn-glycerol-3-phosphate mag + pal → dag PLSc MG212 acyltransferase 2.7.7.41 phosphatidate cytidyltransferase dag + ctp → cdp-dag + pp CDS MG437 cdp-dag + ser → pser + 2.7.8.8 phosphatidylserine synthase PSS n.i. cmp 4.1.1.65 phosphatidylserine decarboxylase pser → peta PSD n.i.
    [Show full text]
  • Coupled Nucleoside Phosphorylase Reactions in Escherichia Coli John Lewis Ott Iowa State College
    Iowa State University Capstones, Theses and Retrospective Theses and Dissertations Dissertations 1956 Coupled nucleoside phosphorylase reactions in Escherichia coli John Lewis Ott Iowa State College Follow this and additional works at: https://lib.dr.iastate.edu/rtd Part of the Biochemistry Commons, and the Microbiology Commons Recommended Citation Ott, John Lewis, "Coupled nucleoside phosphorylase reactions in Escherichia coli " (1956). Retrospective Theses and Dissertations. 13758. https://lib.dr.iastate.edu/rtd/13758 This Dissertation is brought to you for free and open access by the Iowa State University Capstones, Theses and Dissertations at Iowa State University Digital Repository. It has been accepted for inclusion in Retrospective Theses and Dissertations by an authorized administrator of Iowa State University Digital Repository. For more information, please contact [email protected]. NOTE TO USERS This reproduction is the best copy available. UMI COUPLED NUCLEOSIDE PHOSPHORYLASE REACTIONS IN ESCHERICHIA COLI / by John Lewis Ott A Dissertation Submitted to the Graduate Faculty in Partial Fulfillment of The Requirements for the Degree of DOCTOR OF PHILOSOPHY Major Subject: Physlolgglcal Bacteriology Approved: Signature was redacted for privacy. In Charge of Major Work Signature was redacted for privacy. Head of Major Department Signature was redacted for privacy. Dean of Graduate College Iowa State College 1956 UMI Number: DP12892 INFORMATION TO USERS The quality of this reproduction is dependent upon the quality of the copy submitted. Broken or indistinct print, colored or poor quality illustrations and photographs, print bleed-through, substandard margins, and improper alignment can adversely affect reproduction. In the unlikely event that the author did not send a complete manuscript and there are missing pages, these will be noted.
    [Show full text]