Ketoadipic Aciduria: a Description of a New Metabolic Error in Lysine - Tryptophan Degradation
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Effect of Propionic Acid on Fatty Acid Oxidation and U Reagenesis
Pediat. Res. 10: 683- 686 (1976) Fatty degeneration propionic acid hyperammonemia propionic acidemia liver ureagenesls Effect of Propionic Acid on Fatty Acid Oxidation and U reagenesis ALLEN M. GLASGOW(23) AND H. PET ER C HASE UniversilY of Colorado Medical Celller, B. F. SlOlillsky LaboralOries , Denver, Colorado, USA Extract phosphate-buffered salin e, harvested with a brief treatment wi th tryps in- EDTA, washed twice with ph os ph ate-buffered saline, and Propionic acid significantly inhibited "CO z production from then suspended in ph os ph ate-buffe red saline (145 m M N a, 4.15 [I-"ejpalmitate at a concentration of 10 11 M in control fibroblasts m M K, 140 m M c/, 9.36 m M PO" pH 7.4) . I n mos t cases the cells and 100 11M in methyl malonic fibroblasts. This inhibition was we re incubated in 3 ml phosph ate-bu ffered sa lin e cont aining 0.5 similar to that produced by 4-pentenoic acid. Methylmalonic acid I1Ci ll-I4Cj palm it ate (19), final concentration approximately 3 11M also inhibited ' 'C0 2 production from [V 'ejpalmitate, but only at a added in 10 II I hexane. Increasing the amount of hexane to 100 II I concentration of I mM in control cells and 5 mM in methyl malonic did not impair palmit ate ox id ation. In two experiments (Fig. 3) the cells. fibroblasts were in cub ated in 3 ml calcium-free Krebs-Ringer Propionic acid (5 mM) also inhibited ureagenesis in rat liver phosphate buffer (2) co nt ain in g 5 g/ 100 ml essent iall y fatty ac id slices when ammonia was the substrate but not with aspartate and free bovine se rum albumin (20), I mM pa lm itate, and the same citrulline as substrates. -
Toxicological Basis Data for the Derivation of EU-LCI Values For
TEXTE 223/2020 Toxicological basis data for the derivation of EU- LCI values for neopentyl glycol, diisobutyl succinate, diisobutyl glutarate, 1,2- dimethoxyethane and 1,2-diethoxyethane Final report German Environment Agency TEXTE 223/2020 Ressortforschungsplan of the Federal Ministry for the Enviroment, Nature Conservation and Nuclear Safety Project No. (FKZ) 3719 62 205 0 Report No. FB000359/ENG Toxicological basis data for the derivation of EU-LCI values for neopentyl glycol, diisobutyl succinate, diisobutyl glutarate, 1,2- dimethoxyethane and 1,2-diethoxyethane Final report by Dr. Barbara Werschkun Wissenschaftsbüro, Berlin On behalf of the German Environment Agency Imprint Publisher Umweltbundesamt Wörlitzer Platz 1 06844 Dessau-Roßlau Tel: +49 340-2103-0 Fax: +49 340-2103-2285 [email protected] Internet: www.umweltbundesamt.de /umweltbundesamt.de /umweltbundesamt Report performed by: Wissenschaftsbüro Dr. Barbara Werschkun Monumentenstr. 31a 10829 Berlin Germany Report completed in: May 2020 Edited by: Section II 1.3 Indoor Hygiene, Health-related Environmental Impacts Dr. Ana Maria Scutaru Publication as pdf: http://www.umweltbundesamt.de/publikationen ISSN 1862-4804 Dessau-Roßlau, December 2020 The responsibility for the content of this publication lies with the author(s). TEXTE Toxicological basis data for the derivation of EU-LCI values for neopentyl glycol, diisobutyl succinate, diisobutyl glutarate, 1,2-dimethoxyethane and 1,2-diethoxyethane – Final report Abstract: Toxicological basis data for the derivation of EU-LCI values for neopentyl glycol, diisobutyl succinate, diisobutyl glutarate, 1,2-dimethoxyethane and 1,2-diethoxyethane The objective of this study was the evaluation of toxicological data for five substances as basis for the derivation of EU-LCI values. -
Glutaric Aciduria Lactic Acidosis Glutaryl-Coa Dehydrogenase Deficiency Short-Chain Monocarboxylic Acids
Pediat. Res. 13: 977-981 (1979) C6-C l~-dicarboxylicacid ketosis glutaric aciduria lactic acidosis glutaryl-CoA dehydrogenase deficiency short-chain monocarboxylic acids Ketotic Episodes in Glutaryl-CoA Dehydrogenase Deficiency (Glutaric Aciduria) NIELS GREGERSEN AND NIELS JACOB BRANDT Research Laboratory for Metabolic Disorders, University Department of Clinical Chemistry, Aarhus Kommunehospital, Aarhus, and Section of Clinical Genetics, University Department of Paediatrics, Obstetrics, and Gynaecology, Rigshospitalet, Copenhagen, Denmark Summaw the ketoacidosis, a pronounced lactic acidosis and lactic aciduria is seen in most cases. The present report, together with a recent A 7-yr-old boy with glutaryl-CoA dehydrogenase deficiency (glu- report of Goodman et al. (7), indicates that glutaryl-CoA dehy- taric aciduria), presenting periodic episodes of lethargy and keto- drogenase deficiency (glutaric aciduria) may present ketotic epi- sis, was studied during two such episodes. The urinary excretions sodes, similar to those of the other organic acidurias. of glutaric and 3-OH-glutaric acids were 3100-7900 and 460-660 The patient described by Goodman et al. (7) died in a Reye's &mg creatinine, respectively, during these episodes. Urine sam- syndromelike state. Our patient has had two episodes of ketosis ples collected before and after the attacks contained 100-5300 and and lethargy. During these episodes, the urinary metabolic profiles 230-370 &mg creatinine of glutaric acid and 3-OH-glutaric of organic acids were studied in detail, in an attempt to elucidate acids, respectively. During the episodes, glutaconic acid excretion the pathogenic mechanism leading to the severe clinical and rose from 14-89 to 93-630 pg/mg creatinine. -
Untargeted Metabolomics Uncovers the Essential Lysine Transporter in Toxoplasma Gondii
H OH metabolites OH Article Untargeted Metabolomics Uncovers the Essential Lysine Transporter in Toxoplasma gondii Joachim Kloehn 1,*,† , Matteo Lunghi 1,†, Emmanuel Varesio 2 , David Dubois 1 and Dominique Soldati-Favre 1,* 1 Department of Microbiology and Molecular Medicine, University of Geneva, CMU, Rue Michel-Servet 1, 1211 Geneva, Switzerland; [email protected] (M.L.); [email protected] (D.D.) 2 Institute of Pharmaceutical Sciences of Western Switzerland, School of Pharmaceutical Sciences, Mass Spectrometry Core Facility (MZ 2.0), University of Geneva, 1211 Geneva, Switzerland; [email protected] * Correspondence: [email protected] (J.K.); [email protected] (D.S.-F.); Tel.: +41-22-379-57-16 (J.K.); +41-22-379-56-72 (D.S.-F.) † These authors contributed equally to the work. Abstract: Apicomplexan parasites are responsible for devastating diseases, including malaria, toxo- plasmosis, and cryptosporidiosis. Current treatments are limited by emerging resistance to, as well as the high cost and toxicity of existing drugs. As obligate intracellular parasites, apicomplexans rely on the uptake of many essential metabolites from their host. Toxoplasma gondii, the causative agent of tox- oplasmosis, is auxotrophic for several metabolites, including sugars (e.g., myo-inositol), amino acids (e.g., tyrosine), lipidic compounds and lipid precursors (cholesterol, choline), vitamins, cofactors (thiamine) and others. To date, only few apicomplexan metabolite transporters have been charac- terized and assigned a substrate. Here, we set out to investigate whether untargeted metabolomics can be used to identify the substrate of an uncharacterized transporter. Based on existing genome- Citation: Kloehn, J.; Lunghi, M.; and proteome-wide datasets, we have identified an essential plasma membrane transporter of the Varesio, E.; Dubois, D.; Soldati-Favre, major facilitator superfamily in T. -
Inherited Metabolic Disease
Inherited metabolic disease Dr Neil W Hopper SRH Areas for discussion • Introduction to IEMs • Presentation • Initial treatment and investigation of IEMs • Hypoglycaemia • Hyperammonaemia • Other presentations • Management of intercurrent illness • Chronic management Inherited Metabolic Diseases • Result from a block to an essential pathway in the body's metabolism. • Huge number of conditions • All rare – very rare (except for one – 1:500) • Presentation can be non-specific so index of suspicion important • Mostly AR inheritance – ask about consanguinity Incidence (W. Midlands) • Amino acid disorders (excluding phenylketonuria) — 18.7 per 100,000 • Phenylketonuria — 8.1 per 100,000 • Organic acidemias — 12.6 per 100,000 • Urea cycle diseases — 4.5 per 100,000 • Glycogen storage diseases — 6.8 per 100,000 • Lysosomal storage diseases — 19.3 per 100,000 • Peroxisomal disorders — 7.4 per 100,000 • Mitochondrial diseases — 20.3 per 100,000 Pathophysiological classification • Disorders that result in toxic accumulation – Disorders of protein metabolism (eg, amino acidopathies, organic acidopathies, urea cycle defects) – Disorders of carbohydrate intolerance – Lysosomal storage disorders • Disorders of energy production, utilization – Fatty acid oxidation defects – Disorders of carbohydrate utilization, production (ie, glycogen storage disorders, disorders of gluconeogenesis and glycogenolysis) – Mitochondrial disorders – Peroxisomal disorders IMD presentations • ? IMD presentations • Screening – MCAD, PKU • Progressive unexplained neonatal -
Microwave-Assisted Low-Temperature Dehydration Polycondensation of Dicarboxylic Acids and Diols
Polymer Journal (2011) 43, 1003–1007 & The Society of Polymer Science, Japan (SPSJ) All rights reserved 0032-3896/11 $32.00 www.nature.com/pj RAPID COMMUNICATION Microwave-assisted low-temperature dehydration polycondensation of dicarboxylic acids and diols Polymer Journal (2011) 43, 1003–1007; doi:10.1038/pj.2011.107; published online 26 October 2011 INTRODUCTION time (4100 h). Therefore, we next focused on has been no report concerning a Currently, because of increasing concerns identifying more active catalysts and found that non-thermal effect in microwave-assisted about damage to the environment, the devel- scandium and thulium bis(nonafluorobutane- polycondensation reactions,33,34 although opment of new, eco-friendly (industrially sulfonyl)imide ((Sc(NNf2)3) and (Tm(NNf2)3)) there has been a report that non-thermal relevant) chemical reactions and materials is were more efficient catalysts and allowed us microwaves have a role in the chain polymer- crucial. Aliphatic polyesters have attracted to obtain high-molecular-weight polyesters ization of a lactone.32 Therefore, we studied 4 much interest as environmentally benign, (Mn42.0Â10 ) from adipic acid (AdA) and microwave-assisted syntheses of polyesters at biodegradable polymers.1,2 In general, alipha- 3-methyl-1,5-pentanediol (MPD) at 60 1Cina a relatively low temperature (80 1C) using a tic polyesters are commercially produced by shortperiodoftime(24h)andwithasmaller microwave chamber equipped with a tem- polycondensation of a dicarboxylic acid and a amount of catalyst (0.1 mol%) than had pre- perature control, and the results are reported 1.1–1.5 mol excess of a diol at a temperature viously been possible.26 herein. -
Glutaric Acid Production by Systems Metabolic Engineering of an L-Lysine–Overproducing Corynebacterium Glutamicum
Glutaric acid production by systems metabolic engineering of an L-lysine–overproducing Corynebacterium glutamicum Taehee Hana, Gi Bae Kima, and Sang Yup Leea,b,c,1 aMetabolic and Biomolecular Engineering National Research Laboratory, Systems Metabolic Engineering and Systems Healthcare Cross-Generation Collaborative Laboratory, Department of Chemical and Biomolecular Engineering (BK21 Plus Program), Institute for the BioCentury, Korea Advanced Institute of Science and Technology, Yuseong-gu, 34141 Daejeon, Republic of Korea; bBioInformatics Research Center, Korea Advanced Institute of Science and Technology, Yuseong-gu, 34141 Daejeon, Republic of Korea; and cBioProcess Engineering Research Center, Korea Advanced Institute of Science and Technology, Yuseong-gu, 34141, Daejeon, Republic of Korea Contributed by Sang Yup Lee, October 6, 2020 (sent for review August 18, 2020; reviewed by Tae Seok Moon and Blake A. Simmons) There is increasing industrial demand for five-carbon platform processes rely on nonrenewable and toxic starting materials, chemicals, particularly glutaric acid, a widely used building block however. Thus, various approaches have been taken to biologi- chemical for the synthesis of polyesters and polyamides. Here we cally produce glutaric acid from renewable resources (13–19). report the development of an efficient glutaric acid microbial pro- Naturally, glutaric acid is a metabolite of L-lysine catabolism in ducer by systems metabolic engineering of an L-lysine–overproducing Pseudomonas species, in which L-lysine is converted to glutaric Corynebacterium glutamicum BE strain. Based on our previous study, acid by the 5-aminovaleric acid (AVA) pathway (20, 21). We an optimal synthetic metabolic pathway comprising Pseudomonas previously reported the development of the first glutaric acid- putida L-lysine monooxygenase (davB) and 5-aminovaleramide amido- producing Escherichia coli by introducing this pathway compris- hydrolase (davA) genes and C. -
Hydroxy–Methyl Butyrate (HMB) As an Epigenetic Regulator in Muscle
H OH metabolites OH Communication The Leucine Catabolite and Dietary Supplement β-Hydroxy-β-Methyl Butyrate (HMB) as an Epigenetic Regulator in Muscle Progenitor Cells Virve Cavallucci 1,2,* and Giovambattista Pani 1,2,* 1 Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Roma, Italy 2 Institute of General Pathology, Università Cattolica del Sacro Cuore, 00168 Roma, Italy * Correspondence: [email protected] (V.C.); [email protected] (G.P.) Abstract: β-Hydroxy-β-Methyl Butyrate (HMB) is a natural catabolite of leucine deemed to play a role in amino acid signaling and the maintenance of lean muscle mass. Accordingly, HMB is used as a dietary supplement by sportsmen and has shown some clinical effectiveness in preventing muscle wasting in cancer and chronic lung disease, as well as in age-dependent sarcopenia. However, the molecular cascades underlying these beneficial effects are largely unknown. HMB bears a significant structural similarity with Butyrate and β-Hydroxybutyrate (βHB), two compounds recognized for important epigenetic and histone-marking activities in multiple cell types including muscle cells. We asked whether similar chromatin-modifying actions could be assigned to HMB as well. Exposure of murine C2C12 myoblasts to millimolar concentrations of HMB led to an increase in global histone acetylation, as monitored by anti-acetylated lysine immunoblotting, while preventing myotube differentiation. In these effects, HMB resembled, although with less potency, the histone Citation: Cavallucci, V.; Pani, G. deacetylase (HDAC) inhibitor Sodium Butyrate. However, initial studies did not confirm a direct The Leucine Catabolite and Dietary inhibitory effect of HMB on HDACs in vitro. β-Hydroxybutyrate, a ketone body produced by the Supplement β-Hydroxy-β-Methyl liver during starvation or intense exercise, has a modest effect on histone acetylation of C2C12 Butyrate (HMB) as an Epigenetic Regulator in Muscle Progenitor Cells. -
Metabolomic Analysis Reveals That the Drosophila Gene Lysine Influences Diverse Aspects of Metabolism
Genetics: Early Online, published on October 6, 2017 as 10.1534/genetics.117.300201 Metabolomic analysis reveals that the Drosophila gene lysine influences diverse aspects of metabolism Samantha L. St. Clair*‡, Hongde Li*‡, Usman Ashraf†, Jonathan A. Karty†, and Jason M. *§ Tennessen * Department of Biology, Indiana University, Bloomington, IN 47405, USA † Department of Chemistry, Indiana University, Bloomington, IN, 47405, USA. ‡ These authors contributed equally to this work. § Correspondence: [email protected] Keywords: Drosophila, metabolomics, lysine, LKRSDH, familial hyperlysinemia 1 Copyright 2017. ABSTRACT The fruit fly Drosophila melanogaster has emerged as a powerful model for investigating the molecular mechanisms that regulate animal metabolism. A major limitation of these studies, however, is that many metabolic assays are tedious, dedicated to analyzing a single molecule, and rely on indirect measurements. As a result, Drosophila geneticists commonly use candidate gene approaches, which, while important, bias studies towards known metabolic regulators. In an effort to expand the scope of Drosophila metabolic studies, we used the classic mutant lysine (lys) to demonstrate how a modern metabolomics approach can be used to conduct forward genetic studies. Using an inexpensive and well-established gas chromatography-mass spectrometry (GC-MS)-based method, we genetically mapped and molecularly characterized lys by using free lysine levels as a phenotypic readout. Our efforts revealed that lys encodes the Drosophila homolog of Lysine Ketoglutarate Reductase/Saccharopine Dehydrogenase (LKRSDH), which is required for the enzymatic degradation of lysine. Furthermore, this approach also allowed us to simultaneously survey a large swath of intermediate metabolism, thus demonstrating that Drosophila lysine catabolism is complex and capable of influencing seemingly unrelated metabolic pathways. -
Amino Acid Disorders
471 Review Article on Inborn Errors of Metabolism Page 1 of 10 Amino acid disorders Ermal Aliu1, Shibani Kanungo2, Georgianne L. Arnold1 1Children’s Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; 2Western Michigan University Homer Stryker MD School of Medicine, Kalamazoo, MI, USA Contributions: (I) Conception and design: S Kanungo, GL Arnold; (II) Administrative support: S Kanungo; (III) Provision of study materials or patients: None; (IV) Collection and assembly of data: E Aliu, GL Arnold; (V) Data analysis and interpretation: None; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors. Correspondence to: Georgianne L. Arnold, MD. UPMC Children’s Hospital of Pittsburgh, 4401 Penn Avenue, Suite 1200, Pittsburgh, PA 15224, USA. Email: [email protected]. Abstract: Amino acids serve as key building blocks and as an energy source for cell repair, survival, regeneration and growth. Each amino acid has an amino group, a carboxylic acid, and a unique carbon structure. Human utilize 21 different amino acids; most of these can be synthesized endogenously, but 9 are “essential” in that they must be ingested in the diet. In addition to their role as building blocks of protein, amino acids are key energy source (ketogenic, glucogenic or both), are building blocks of Kreb’s (aka TCA) cycle intermediates and other metabolites, and recycled as needed. A metabolic defect in the metabolism of tyrosine (homogentisic acid oxidase deficiency) historically defined Archibald Garrod as key architect in linking biochemistry, genetics and medicine and creation of the term ‘Inborn Error of Metabolism’ (IEM). The key concept of a single gene defect leading to a single enzyme dysfunction, leading to “intoxication” with a precursor in the metabolic pathway was vital to linking genetics and metabolic disorders and developing screening and treatment approaches as described in other chapters in this issue. -
Effect of Ph on the Binding of Sodium, Lysine, and Arginine Counterions to L- Undecyl Leucinate Micelles
Effect of pH on the Binding of Sodium, Lysine, and Arginine Counterions to l- Undecyl Leucinate Micelles Corbin Lewis, Burgoyne H. Hughes, Mariela Vasquez, Alyssa M. Wall, Victoria L. Northrup, Tyler J. Witzleb, Eugene J. Billiot, et al. Journal of Surfactants and Detergents ISSN 1097-3958 Volume 19 Number 6 J Surfact Deterg (2016) 19:1175-1188 DOI 10.1007/s11743-016-1875-y 1 23 Your article is protected by copyright and all rights are held exclusively by AOCS. This e- offprint is for personal use only and shall not be self-archived in electronic repositories. If you wish to self-archive your article, please use the accepted manuscript version for posting on your own website. You may further deposit the accepted manuscript version in any repository, provided it is only made publicly available 12 months after official publication or later and provided acknowledgement is given to the original source of publication and a link is inserted to the published article on Springer's website. The link must be accompanied by the following text: "The final publication is available at link.springer.com”. 1 23 Author's personal copy J Surfact Deterg (2016) 19:1175–1188 DOI 10.1007/s11743-016-1875-y ORIGINAL ARTICLE Effect of pH on the Binding of Sodium, Lysine, and Arginine Counterions to L-Undecyl Leucinate Micelles 1 2 1 2 Corbin Lewis • Burgoyne H. Hughes • Mariela Vasquez • Alyssa M. Wall • 2 2 1 3 Victoria L. Northrup • Tyler J. Witzleb • Eugene J. Billiot • Yayin Fang • 1 2 Fereshteh H. Billiot • Kevin F. Morris Received: 20 May 2016 / Accepted: 6 September 2016 / Published online: 20 September 2016 Ó AOCS 2016 Abstract Micelle formation by the amino acid-based sur- surface through both of its amine functional groups. -
APPENDIX G Acid Dissociation Constants
harxxxxx_App-G.qxd 3/8/10 1:34 PM Page AP11 APPENDIX G Acid Dissociation Constants § ϭ 0.1 M 0 ؍ (Ionic strength ( † ‡ † Name Structure* pKa Ka pKa ϫ Ϫ5 Acetic acid CH3CO2H 4.756 1.75 10 4.56 (ethanoic acid) N ϩ H3 ϫ Ϫ3 Alanine CHCH3 2.344 (CO2H) 4.53 10 2.33 ϫ Ϫ10 9.868 (NH3) 1.36 10 9.71 CO2H ϩ Ϫ5 Aminobenzene NH3 4.601 2.51 ϫ 10 4.64 (aniline) ϪO SNϩ Ϫ4 4-Aminobenzenesulfonic acid 3 H3 3.232 5.86 ϫ 10 3.01 (sulfanilic acid) ϩ NH3 ϫ Ϫ3 2-Aminobenzoic acid 2.08 (CO2H) 8.3 10 2.01 ϫ Ϫ5 (anthranilic acid) 4.96 (NH3) 1.10 10 4.78 CO2H ϩ 2-Aminoethanethiol HSCH2CH2NH3 —— 8.21 (SH) (2-mercaptoethylamine) —— 10.73 (NH3) ϩ ϫ Ϫ10 2-Aminoethanol HOCH2CH2NH3 9.498 3.18 10 9.52 (ethanolamine) O H ϫ Ϫ5 4.70 (NH3) (20°) 2.0 10 4.74 2-Aminophenol Ϫ 9.97 (OH) (20°) 1.05 ϫ 10 10 9.87 ϩ NH3 ϩ ϫ Ϫ10 Ammonia NH4 9.245 5.69 10 9.26 N ϩ H3 N ϩ H2 ϫ Ϫ2 1.823 (CO2H) 1.50 10 2.03 CHCH CH CH NHC ϫ Ϫ9 Arginine 2 2 2 8.991 (NH3) 1.02 10 9.00 NH —— (NH2) —— (12.1) CO2H 2 O Ϫ 2.24 5.8 ϫ 10 3 2.15 Ϫ Arsenic acid HO As OH 6.96 1.10 ϫ 10 7 6.65 Ϫ (hydrogen arsenate) (11.50) 3.2 ϫ 10 12 (11.18) OH ϫ Ϫ10 Arsenious acid As(OH)3 9.29 5.1 10 9.14 (hydrogen arsenite) N ϩ O H3 Asparagine CHCH2CNH2 —— —— 2.16 (CO2H) —— —— 8.73 (NH3) CO2H *Each acid is written in its protonated form.