SUPPORT GUIDE Contents ORGANIC ACIDS OXIDATIVE STRESS MARKERS AMINO ACIDS FATTY ACIDS TOXIC and NUTRIENT ELEMENTS
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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. -
Methylmalonic Methylmalonic Aciduria
12/27/2008 METHYLMALONIC ACIDURIA Marc E. Tischler, PhD; University of Arizona METHYLMALONIC ACIDURIA •methylmalonyl-coenzyme A (methylmalonyl-CoA) is formed during the breakdown of some amino acids (i.e., isoleucine, valine, methionine, threonine) and fatty acids that contain an odd number of carbons (small fraction of total) (Figure 1) •methylmalonyl-CoA is further metabolized: o methylmalonyl-CoA mutase produces succinyl-CoA and requires a modified form of vitamin B12 (adenosyl-B12) o succinyl-CoA enters the citric acid cycle whose function is primarily to produce usable energy in the cell • deficiency of methylmalonyl-CoA mutase prevents the metabolism of methylmalonyl- CoA leading to excessive formation of methylmalonic acid o excessive methylmalonic acid is excreted in the urine causing methylmalonic aciduria o potentially life-threatening because it creates an acidic condition (acidosis) •treatment: o restricting intake of the 4 amino acids o neutralizing the acidosis o providing vitamin B12 to potentially boost the activity of methylmalonyl-CoA mutase 1 12/27/2008 NORMAL DISEASE Methionine, Isoleucine, Methionine, Isoleucine, Valine, Threonine, Valine, Threonine, Odd-chain fatty acids Odd-chain fatty acids Many various enzymes Propionyl-CoA Propionyl-CoA Propypionyl-CoA carboxylase Methylmalonyl-CoA Methylmalonyl-CoA Methylmalonyl- +adenosyl-B12 CoA mutase Succinyl-CoA Succinyl-CoAX Enzyme names for Citric Methylmalonic acid Usable indicated arrow Acid acidosis Cycle energy Figure 1. Metabolism of 4 amino acids and odd-chain fatty acids all proceed via methylmalonyl-CoA. Methylmalonyl- CoA is metabolized to succinyl-CoA that enters the citric acid cycle, which produces usable energy for the cell. In methylmalonic aciduria, methylmalonyl-CoA mutase is deficient (X) so that methylmalonyl-CoA accumulates. -
Measurement of Metabolite Variations and Analysis of Related Gene Expression in Chinese Liquorice (Glycyrrhiza Uralensis) Plants
www.nature.com/scientificreports OPEN Measurement of metabolite variations and analysis of related gene expression in Chinese liquorice Received: 15 March 2017 Accepted: 28 March 2018 (Glycyrrhiza uralensis) plants under Published: xx xx xxxx UV-B irradiation Xiao Zhang1,2, Xiaoli Ding3,4, Yaxi Ji1,2, Shouchuang Wang5, Yingying Chen1,2, Jie Luo5, Yingbai Shen1,2 & Li Peng3,4 Plants respond to UV-B irradiation (280–315 nm wavelength) via elaborate metabolic regulatory mechanisms that help them adapt to this stress. To investigate the metabolic response of the medicinal herb Chinese liquorice (Glycyrrhiza uralensis) to UV-B irradiation, we performed liquid chromatography tandem mass spectrometry (LC-MS/MS)-based metabolomic analysis, combined with analysis of diferentially expressed genes in the leaves of plants exposed to UV-B irradiation at various time points. Fifty-four metabolites, primarily amino acids and favonoids, exhibited changes in levels after the UV-B treatment. The amino acid metabolism was altered by UV-B irradiation: the Asp family pathway was activated and closely correlated to Glu. Some amino acids appeared to be converted into antioxidants such as γ-aminobutyric acid and glutathione. Hierarchical clustering analysis revealed that various favonoids with characteristic groups were induced by UV-B. In particular, the levels of some ortho- dihydroxylated B-ring favonoids, which might function as scavengers of reactive oxygen species, increased in response to UV-B treatment. In general, unigenes encoding key enzymes involved in amino acid metabolism and favonoid biosynthesis were upregulated by UV-B irradiation. These fndings lay the foundation for further analysis of the mechanism underlying the response of G. -
Propionic Acidemia: an Extremely Rare Cause of Hemophagocytic Lymphohistiocytosis in an Infant
Case report Arch Argent Pediatr 2020;118(2):e174-e177 / e174 Propionic acidemia: an extremely rare cause of hemophagocytic lymphohistiocytosis in an infant Sultan Aydin Kökera, MD, Osman Yeşilbaşb, MD, Alper Kökerc, MD, and Esra Şevketoğlud, Assoc. Prof. ABSTRACT INTRODUCTION Hemophagocytic lymphohystiocytosis (HLH) may be primary Hemophagocytic lymphohistiocytosis (inherited/familial) or secondary to infections, malignancies, rheumatologic disorders, immune deficiency syndromes (HLH) is a life-threatening disorder in and metabolic diseases. Cases including lysinuric protein which there is uncontrolled proliferation of intolerance, multiple sulfatase deficiency, galactosemia, activated lymphocytes and histiocytes. The Gaucher disease, Pearson syndrome, and galactosialidosis have diagnosis of HLH is based on fulfilling at least previously been reported. It is unclear how the metabolites trigger HLH in metabolic diseases. A 2-month-old infant five of eight criteria (fever, splenomegaly, with lethargy, pallor, poor feeding, hepatosplenomegaly, bicytopenia, hypertriglyceridemia and/ fever and pancytopenia, was diagnosed with HLH and the or hypofibrinogenemia, hemophagocytosis, HLH-2004 treatment protocol was initiated. Analysis for low/absent natural killer cell activity, primary HLH gene mutations and metabolic screening tests were performed together; primary HLH gene mutations were hyperferritinemia, and high soluble interleukin- negative, but hyperammonemia and elevated methyl citrate 2-receptor levels). HLH includes both familial were detected. Propionic acidemia was diagnosed with tandem and reactive disease triggered by infection, mass spectrometry in neonatal dried blood spot. We report this immunologic disorder, malignancy, or drugs. case of HLH secondary to propionic acidemia. Both metabolic disorder screening tests and gene mutation analysis may be Clinical presentations of patients with primary performed simultaneously especially for early diagnosis in (familial) and secondary (reactive) HLH are infants presenting with HLH. -
Eicosanoids in Carcinogenesis
4open 2019, 2,9 © B.L.D.M. Brücher and I.S. Jamall, Published by EDP Sciences 2019 https://doi.org/10.1051/fopen/2018008 Special issue: Disruption of homeostasis-induced signaling and crosstalk in the carcinogenesis paradigm “Epistemology of the origin of cancer” Available online at: Guest Editor: Obul R. Bandapalli www.4open-sciences.org REVIEW ARTICLE Eicosanoids in carcinogenesis Björn L.D.M. Brücher1,2,3,*, Ijaz S. Jamall1,2,4 1 Theodor-Billroth-Academy®, Germany, USA 2 INCORE, International Consortium of Research Excellence of the Theodor-Billroth-Academy®, Germany, USA 3 Department of Surgery, Carl-Thiem-Klinikum, Cottbus, Germany 4 Risk-Based Decisions Inc., Sacramento, CA, USA Received 21 March 2018, Accepted 16 December 2018 Abstract- - Inflammation is the body’s reaction to pathogenic (biological or chemical) stimuli and covers a burgeoning list of compounds and pathways that act in concert to maintain the health of the organism. Eicosanoids and related fatty acid derivatives can be formed from arachidonic acid and other polyenoic fatty acids via the cyclooxygenase and lipoxygenase pathways generating a variety of pro- and anti-inflammatory mediators, such as prostaglandins, leukotrienes, lipoxins, resolvins and others. The cytochrome P450 pathway leads to the formation of hydroxy fatty acids, such as 20-hydroxyeicosatetraenoic acid, and epoxy eicosanoids. Free radical reactions induced by reactive oxygen and/or nitrogen free radical species lead to oxygenated lipids such as isoprostanes or isolevuglandins which also exhibit pro-inflammatory activities. Eicosanoids and their metabolites play fundamental endocrine, autocrine and paracrine roles in both physiological and pathological signaling in various diseases. These molecules induce various unsaturated fatty acid dependent signaling pathways that influence crosstalk, alter cell–cell interactions, and result in a wide spectrum of cellular dysfunctions including those of the tissue microenvironment. -
Part One Amino Acids As Building Blocks
Part One Amino Acids as Building Blocks Amino Acids, Peptides and Proteins in Organic Chemistry. Vol.3 – Building Blocks, Catalysis and Coupling Chemistry. Edited by Andrew B. Hughes Copyright Ó 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim ISBN: 978-3-527-32102-5 j3 1 Amino Acid Biosynthesis Emily J. Parker and Andrew J. Pratt 1.1 Introduction The ribosomal synthesis of proteins utilizes a family of 20 a-amino acids that are universally coded by the translation machinery; in addition, two further a-amino acids, selenocysteine and pyrrolysine, are now believed to be incorporated into proteins via ribosomal synthesis in some organisms. More than 300 other amino acid residues have been identified in proteins, but most are of restricted distribution and produced via post-translational modification of the ubiquitous protein amino acids [1]. The ribosomally encoded a-amino acids described here ultimately derive from a-keto acids by a process corresponding to reductive amination. The most important biosynthetic distinction relates to whether appropriate carbon skeletons are pre-existing in basic metabolism or whether they have to be synthesized de novo and this division underpins the structure of this chapter. There are a small number of a-keto acids ubiquitously found in core metabolism, notably pyruvate (and a related 3-phosphoglycerate derivative from glycolysis), together with two components of the tricarboxylic acid cycle (TCA), oxaloacetate and a-ketoglutarate (a-KG). These building blocks ultimately provide the carbon skeletons for unbranched a-amino acids of three, four, and five carbons, respectively. a-Amino acids with shorter (glycine) or longer (lysine and pyrrolysine) straight chains are made by alternative pathways depending on the available raw materials. -
Bacterial Dissimilation of Citric Acid Carl Robert Brewer Iowa State College
Iowa State University Capstones, Theses and Retrospective Theses and Dissertations Dissertations 1939 Bacterial dissimilation of citric acid Carl Robert Brewer Iowa State College Follow this and additional works at: https://lib.dr.iastate.edu/rtd Part of the Microbiology Commons Recommended Citation Brewer, Carl Robert, "Bacterial dissimilation of citric acid " (1939). Retrospective Theses and Dissertations. 13227. https://lib.dr.iastate.edu/rtd/13227 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]. INFORMATION TO USERS This manuscript has been reproduced from the microfilm master. UMI films the text directly from the original or copy submitted. Thus, some thesis and dissertation copies are in typewriter face, while others may be from any type of computer printer. The quality of this reproduction is dependent upon the quality of the copy submitted. Brol<en or indistinct print, colored or poor quality illustrations and photographs, print bleedthrough, substandard margins, and improper alignment can adversely affect reproduction. In the unlikely event that the author did not send UMI a complete manuscript and there are missing pages, these will be noted. Also, if unauthorized copyright material had to be removed, a note will indicate the deletion. Oversize materials (e.g., maps, drawings, charts) are reproduced by sectioning the original, beginning at the upper left-hand comer and continuing from left to right in equal sections with small overlaps. -
Aconitic Acid from Sugarcane
Louisiana State University LSU Digital Commons LSU Doctoral Dissertations Graduate School 2007 Aconitic acid from sugarcane: production and industrial application Nicolas Javier Gil Zapata Louisiana State University and Agricultural and Mechanical College, [email protected] Follow this and additional works at: https://digitalcommons.lsu.edu/gradschool_dissertations Part of the Engineering Science and Materials Commons Recommended Citation Gil Zapata, Nicolas Javier, "Aconitic acid from sugarcane: production and industrial application" (2007). LSU Doctoral Dissertations. 3740. https://digitalcommons.lsu.edu/gradschool_dissertations/3740 This Dissertation is brought to you for free and open access by the Graduate School at LSU Digital Commons. It has been accepted for inclusion in LSU Doctoral Dissertations by an authorized graduate school editor of LSU Digital Commons. For more information, please [email protected]. ACONITIC ACID FROM SUGARCANE: PRODUCTION AND INDUSTRIAL APPLICATION A Dissertation Submitted to the Graduate Faculty of the Louisiana State University and Agricultural and Mechanical College in partial fulfillment of the requirements for the degree of Doctor in Philosophy In The Interdepartmental Program in Engineering Science by Nicolas Javier Gil Zapata B.S., Universidad Industrial de Santander, Colombia, 1988 December, 2007 ACKNOWLEDGEMENTS I sincerely thank my major advisor Dr. Michael Saska for his guidance, assistance, and continuous support throughout my graduate studies at LSU, and for sharing his knowledge and experience of the sugarcane industry. I extend my sincere appreciation to my committee members: Drs. Ioan Negulescu, Benjamin Legendre, Peter Rein, Donal Day, Armando Corripio, for comments, suggestions and critical review of this manuscript. I thank, Dr. Negulescu for introducing me to exciting field of polymers. -
Amino Acid Metabolism: Amino Acid Degradation & Synthesis
Amino Acid Metabolism: Amino Acid Degradation & Synthesis Dr. Diala Abu-Hassan, DDS, PhD All images are taken from Lippincott’s Biochemistry textbook except where noted CATABOLISM OF THE CARBON SKELETONS OF AMINO ACIDS The pathways by which AAs are catabolized are organized according to which one (or more) of the seven intermediates is produced from a particular amino acid. GLUCOGENIC AND KETOGENIC AMINO ACIDS The classification is based on which of the seven intermediates are produced during their catabolism (oxaloacetate, pyruvate, α-ketoglutarate, fumarate, succinyl coenzyme A (CoA), acetyl CoA, and acetoacetate). Glucogenic amino acids catabolism yields pyruvate or one of the TCA cycle intermediates that can be used as substrates for gluconeogenesis in the liver and kidney. Ketogenic amino acids catabolism yields either acetoacetate (a type of ketone bodies) or one of its precursors (acetyl CoA or acetoacetyl CoA). Other ketone bodies are 3-hydroxybutyrate and acetone Amino acids that form oxaloacetate Hydrolysis Transamination Amino acids that form α-ketoglutarate via glutamate 1. Glutamine is converted to glutamate and ammonia by the enzyme glutaminase. Glutamate is converted to α-ketoglutarate by transamination, or through oxidative deamination by glutamate dehydrogenase. 2. Proline is oxidized to glutamate. 3. Arginine is cleaved by arginase to produce Ornithine (in the liver as part of the urea cycle). Ornithine is subsequently converted to α-ketoglutarate. Amino acids that form α-ketoglutarate via glutamate 4. Histidine is oxidatively deaminated by histidase to urocanic acid, which then forms N-formimino glutamate (FIGlu). Individuals deficient in folic acid excrete high amounts of FIGlu in the urine FIGlu excretion test has been used in diagnosing a deficiency of folic acid. -
Essential Fatty Acid and Cell Culture: Where We Stand
Essential Fatty Acid And Cell Culture: Where We Stand Phone: +1 418.874.0054 Toll Free: 1 877.SILICYCLE (North America only) Fax : +1 418.874.0355 [email protected] www.SiliCycle.com SiliCycle Inc - Worldwide Headquarters 2500, Parc-Technologique Blvd Quebec City (Quebec) G1P 4S6 CANADA Tissue engineering aims at creating relevant human in vitro models for evaluation of drugs or for transplantation. Those models are intended to be as physiological as possible. However, essential fatty acids are currently ignored in the process. Essential for proper membrane fluidity, these lipidic building-blocks are also implicated in several cellular processes, including cell signaling. In fact, the beneficial effects of a proper omega-3 diet were clearly established in several clinical studies for a large array of pathological conditions including cardiovascular diseases, diabetes, chronic inflammation and neurodegenerative diseases. Ultimately, these in vivo effects are orchestrated at the cellular level; hence supplementation with essentials fatty acids is becoming paramount for cell culture models as it started to emerge. Conditions are met for cell biology to integrate fatty acids in the culture medium and enter the lipidomic era! © SiliCycle inc. 2017 EssentialEssential Fatty fatty Acid acid Production production And and Metabolism metabolism Essential Fatty Acid And Cell Culture: Where Do We Stand pg = prostaglandin tx = thromboxane pgi = protacyclin It = leukotriene Mammalian cells are routinely cultured using the usual basal Omega-3 family Omega-6 family medium that is a bicarbonate-buffered isotonic aqueous = less inflammatory solution, with a high level of glucose supplemented with α-linolenic acid = more inflammatory α-linolenic acid vitamins as well as essential amino acids. -
Hungry for Your Alanine: When Liver Depends on Muscle Proteolysis
The Journal of Clinical Investigation COMMENTARY Hungry for your alanine: when liver depends on muscle proteolysis Theresia Sarabhai1,2 and Michael Roden1,2,3 1Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, Düsseldorf, Germany. 2German Center for Diabetes Research, München-Neuherberg, Germany. 3Division of Endocrinology and Diabetology, Medical Faculty, Heinrich-Heine University Düsseldorf, Düsseldorf, Germany. β-oxidation and the acetyl-CoA pool, which Fasting requires complex endocrine and metabolic interorgan crosstalk, allosterically activates pyruvate carboxylase flux (V ), and which, together with glycerol which involves shifting from glucose to fatty acid oxidation, derived from PC adipose tissue lipolysis, in order to preserve glucose for the brain. The as substrate, maintains the rates of hepatic gluconeogenesis and endogenous glucose glucose-alanine (Cahill) cycle is critical for regenerating glucose. In this issue production (V ) (8). of JCI, Petersen et al. report on their use of an innovative stable isotope EGP tracer method to show that skeletal muscle–derived alanine becomes rate Liver–skeletal muscle controlling for hepatic mitochondrial oxidation and, in turn, for glucose metabolic crosstalk production during prolonged fasting. These results provide new insight Other metabolic pathways are also known into skeletal muscle–liver metabolic crosstalk during the fed-to-fasting to connect skeletal muscle and liver. The transition in humans. Cori -
Methylmalonyl-Coa Mutase Induction by Cerebral Ischemia and Neurotoxicity of the Mitochondrial Toxin Methylmalonic Acid
The Journal of Neuroscience, November 15, 1996, 16(22):7336–7346 Methylmalonyl-CoA Mutase Induction by Cerebral Ischemia and Neurotoxicity of the Mitochondrial Toxin Methylmalonic Acid Purnima Narasimhan, Robert Sklar, Matthew Murrell, Raymond A. Swanson, and Frank R. Sharp Department of Neurology, University of California, San Francisco, San Francisco, California 94143, and Department of Veterans Affairs Medical Center, San Francisco, California 94121 Differential screening of gerbil brain hippocampal cDNA librar- (SDH), produced dose-related cell death when injected into the ies was used to search for genes expressed in ischemic, but basal ganglia of adult rat brain. This neurotoxicity is similar to that not normal, brain. The methylmalonyl-CoA mutase (MCM) of structurally related mitochondrial SDH inhibitors, malonate and cDNA was highly expressed after ischemia and showed a 95% 3-nitropropionic acid. Methylmalonic acid may contribute to neu- similarity to mouse and 91% similarity to the human MCM ronal injury in human conditions in which it accumulates, including cDNAs. Transient global ischemia induced a fourfold increase MCM mutations and B12 deficiency. This study shows that in MCM mRNA on Northern blots from both hippocampus and methylmalonyl-CoA mutase is induced by several stresses, in- whole forebrain. MCM protein exhibited a similar induction on cluding ischemia, and would serve to decrease the accumulation Western blots of gerbil cerebral cortex 8 and 24 hr after isch- of an endogenous cellular mitochondrial inhibitor and neurotoxin, emia. Treatment of primary brain astrocytes with either the methylmalonic acid. branched-chain amino acid (BCAA) isoleucine or the BCAA metabolite, propionate, induced MCM mRNA fourfold. In- creased concentrations of BCAAs and odd-chain fatty acids, Key words: methylmalonic acid; methylmalonyl-CoA mutase; both of which are metabolized to propionate, may contribute to branched-chain amino acids; odd-chain fatty acids; propionate; inducing the MCM gene during ischemia.