DOCSLIB.ORG

Reaction of Polycyclic Hydrocarbon-Cysteine Conjugates with the Aminoacyl-RNA Synthetase System1

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Reaction of Polycyclic Hydrocarbon-Cysteine Conjugates with the Aminoacyl-RNA Synthetase System1 [CANCER RESEARCH 30, 155-161, January 1970] Reaction of Polycyclic Hydrocarbon-Cysteine Conjugates with the Aminoacyl-RNA Synthetase System1 E. T. Bucovaz, J. C. Morrison, H. L. James, C. F. Dais, and J. L. Wood Department of Biochemistry, University of Tennessee Medical Units, Memphis, Tennessee 38103 SUMMARY naphthyl)-L-cysteine and PCP-cysteine2 into microsomal protein of rat liver was reported in earlier communica A number of arylcysteine derivatives, which are metabolites tions from this laboratory (7-9). Subsequently, of polycyclic aromatic hydrocarbons, have been synthesized. we reported that tetrahydrohydroxynaphthylcysteine appears These amino acid analogs were tested for their ability to act to be activated by the valyl and isoleucyl RNA synthetases of as substrates for aminoacyl-RNA synthetases in an in vitro rat liver or yeast, and the conjugate is transferred to the system using enzyme fractions of bakers' yeast. These studies respective species of tRNA of yeast (6). Furthermore, the have shown that 5-(p-chlorophenyl)-L-cysteine, 5-(9 ,10 conjugate was incorporated into ribosomal protein by a dihydro-9-hydroxy-l 0-phenanthryl)-L-cysteine, rat-liver preparation. According to prevailing theories of amino 5-(5 , 6-dihydro-6-hydroxy-5-benz(a)anthryl)-L -cysteine, acid metabolism, tetrahydrohydroxynaphthylcysteine would 5- (5 , 6- dihydro-6-hydroxy-5-dibenz(a , h)anthryl- L-cysteine, be transferred to some of the positions which are normally and S-(7-benz(a)anthryl)-methyl-L-cysteine are activated and occupied by valine and isoleucine in the forming peptide transferred to tRNA. The arylcysteines were observed to chain. compete with a variety of natural amino acids. This investi These findings provide a pathway by which aromatic gation revealed that chlorophenylcysteine competed with hydrocarbons can be bound to specific sites during synthesis arginine; dihydrohydroxyphenanthrylcysteine competed with of protein molecules. The sites are distinct from those glutamic acid, phenylalanine, and histidine for activating involved in direct binding of hydrocarbons or their metab enzymes; dihydrohydroxybenzanthrylcysteine likewise com olites to intact tissue proteins. peted with arginine and phenylalanine; and dihydrohydroxy- Typical cysteine conjugates of chlorobenzene, phenan- dibenzanthrylcysteine competed with methionine and leucine. threne, and the carcinogens methylbenzanthracene and di- Thus, the structure of the hydrocarbon moiety conjugated benzanthracene have been prepared and studied for their with the sulfhydryl group of cysteine determines in behavior in the protein-biosynthesizing system. This paper particular the synthetases involved in amino acid activation. reports the activation and transfer of the hydrocarbon-cys- Moreover none of the cysteine conjugates were activated by teine conjugates to tRNA. Preliminary reports have been the cysteinyl-RNA synthetase. Hydrocarbons are bound to presented (24-26). protein by this pathway at sites different from those resulting from direct interaction. MATERIALS AND METHODS INTRODUCTION Preparation of Enzyme Fractions A, B, and C. Bakers' Protein binding of administered carcinogenic hydrocarbons yeast, 3 Ib, was frozen for 6 to 8 hr in approximately 3 has been well established (16). The implication of such liters of an ether-C02 mixture to break the cells. Before metabolic events in the process of carcinogenesis has been thawing, the excess ether was decanted from the yeast, and inferred (30). This report describes a pathway by which the residual ether was removed by vacuum at room tempera carcinogens as conjugates of amino acids can be bound to ture. The resulting homogenate was cooled to 0—2°,15g proteins via the mechanism utilized for amino acid incor KC1 were added, and the mixture was stirred for 12 to 14 poration. hr. Following the KC1 addition step, the homogenate was The in vitro incorporation of aromatic hydrocarbon- centrifuged at 7,700 X g for 20 min to remove all debris; cysteine conjugates, 5-(l, 2, 3, 4-tetrahydro-2-hydroxy-l - 2The abbreviations used are: tRNA, transfer ribonucleic acid; PPj, This investigation was supported in part by USPHS Research Grant inorganic pyrophospnate; PCP-cysteine, 5-(p-chlorophenyl)-L-cysteine; CA-01228 from the National Cancer Institute and by USPHS DHP-cysteine, 5-(9 ,10-dihydro-9-hydroxy-10-phenanthryl)-L-cysteine; Research Grant AM-09131 from the National Institute of Arthritis DHD-cysteine, S-(5 , 6-dihydro-6-hydroxy-5-dibenz(a , h)anthryl)-L- and Metabolic Diseases. -cysteine; DHB-cysteine, S-(5 ,6-dihydro-6-hydroxy-5-benz(a)an- Received November 22, 1968; accepted June 3, 1969. thryl)-L-cysteine; BM-cysteine, S-(7-benz(a)anthrylmethyl)-L-cysteine. JANUARY 1970 155 Downloaded from cancerres.aacrjournals.org on October 2, 2021. © 1970 American Association for Cancer Research. Bucovaz, Morrison, James, Dais, and Wood the supernatant liquid was filtered through cheesecloth and separated. These were extracted with two 15-ml portions of then centrifuged at 105,000 X g for 1 hr. The volume of the dry benzene at 50°.The residue, 0.4 g, was extracted with 25 supernatant liquid recovered varied between 350 and 375 ml, ml hot methanol. The extract was concentrated to 5 ml and depending upon the water content of the yeast. A series of treated with water. Lustrous crystals separated. The yield of ammonium sulfate precipitation steps followed. Throughout S-(9,10-dihydro-9-hydroxy-10-phenanthryl)-L-cysteine melting these fractionation steps the temperature was maintained at at 171.5-172° (with decomposition) was 0.29 g (62% of the 0—4°.Initially, 15.36 g solid ammonium sulfate were added theoretical amount). Recrystallization did not change the to 300 ml of the crude enzyme fraction. After 3 days the melting point. A paper chromatogram developed with precipitate formed was removed by centrifugation and dis butanol:acetic acid:water (1:2:1) had a single ninhydrin- carded. The supernatant fraction was adjusted to 60% satura positive spot at Rp 0.7. tion upon the addition of 33.3 g ammonium sulfate/100 ml, 5 , 6-Dihydro-5 , 6-epoxybenz(a)anthracene was prepared followed by thorough mixing. After 2 hr, the mixture was according to the procedure of Newman and Blum (28). The centrifuged at 7,700 X g for 20 min. The supernatant layer epoxide, 0.2 g, and 0.23 g of L-cysteine hydrochloride was discarded, and the precipitate was dissolved in 180 ml of monohydrate were reacted essentially as described for the water, resulting in a total volume of 230 to 360 ml phenanthrene conjugate above. A 29% yield of S-(5 ,6- depending on the amount of protein precipitated. This dihydro-6-hydroxy-5-benz(a)anthryl)-L-cysteine melting at preparation was termed the "60% extract." Three fractions 174—175°wasobtained. The elemental analysis values for the were obtained by a second ammonium sulfate fractionation: compound agreed with the theoretical values. Chromatography Fraction B, 0 to 42%; Fraction C, 42 to 50%; and Fraction A, in butanol:acetic acid:water (1:2:1) gave a single spot at RF supernatant fraction equivalent to 50 to 60% saturation. The 0.75. 3 fractions were adjusted to 0.01 M Tris, pH 7.25, and then 2-Phenylphenanthrene-2 , 3-dialdehyde was prepared from dialyzed against Tris of the same concentration and pH to dibenzanthracene by oxidation of the hydrocarbon with remove ammonium sulfate and other small-molecular-weight osmium tetroxide followed by treatment of the resulting diol components. Fractions A, B, and C were used in this with periodate (15). A more efficient procedure resulted from investigation as sources of enzymes. Transfer RNA of Bakers' Yeast. Transfer RNA was ozonolysis of dibenz(a,h)anthracene by the method of Monconi et al. (27). The yield of dialdehyde was 55% of the obtained from the General Biochemicals Company (Chagrin theoretical amount. 5 , 6-Dihydro-5 , 6-epoxydibenz(a,A)an- Falls, Ohio) and was used as the acceptor of the arylcys- thracene was prepared from the dialdehyde. To 0.2 g of the teines and naturally occurring amino acids. dialdehyde in 2 to 3 ml dry benzene was added 0.2 g of Preparation of Pyrophosphate-32P. The K432P2O7 was tris(dimethylamino)phosphine. The system was kept under prepared from carrier-free orthophosphate-32P (New England nitrogen. The mixture was shaken for 5 ml at 55% and then was cooled to 5°to produce crystals. The supernatant liquor Nuclear Corporation, Boston, Mass.) by pyrolysis (19). was decanted. The residue was washed 3 times with cold ATP-PPi of Exchange Reaction. The assays were carried out as described in Table 1. The ATP-32PPj exchange reaction cyclohexane and then recrystallized from cyclohexane: ben zene (70:30) to yield 0.17 g of light green needles. These had was terminated by the addition of 1 ml 10% trichloracetic an indefinite melting point as observed by Boyland and Sims acid. The mixture was briefly centrifuged to remove the (4). The yield of 'product was 88% of the theoretical. precipitated protein, and the ATP was absorbed on Darco 5-(5 , 6-Dihydro-6-hydroxy-5-dibenz(aJi)anthryl-L-cysteine G-60 (Matheson, Coleman and Bell, East Rutherford, N. J.) was prepared from a mixture of L-cysteine hydrochloride according to the method of DeMoss and Novelli (10). monohydrate, 0.6 g, sodium bicarbonate, 0.6 g, and the Preparation of ,s-substituted Cysteines. PCP-cysteine epoxide, 0.3 g, in 20 ml water and 20 ml freshly distilled L-cysteine was prepared by the method of du Vigneaud et al. dioxane. The mixture was stirred for 1.5 hr at 75°and then (12). adjusted to pH 7.0 at room temperature by slow addition of Epoxides were prepared according to the procedure of 5% HC1. When the solution was evaporated to a 50-ml volume and cooled at 5°,it yielded 0.5 g light-tan, solid material.
Load more

Recommended publications
  • Thermal Decomposition of the Amino Acids Glycine, Cysteine, Aspartic Acid, Asparagine, Glutamic Acid, Glutamine, Arginine and Histidine
    bioRxiv preprint doi: https://doi.org/10.1101/119123; this version posted March 22, 2017. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Thermal decomposition of the amino acids glycine, cysteine, aspartic acid, asparagine, glutamic acid, glutamine, arginine and histidine Ingrid M. Weiss*, Christina Muth, Robert Drumm & Helmut O.K. Kirchner INM-Leibniz Institute for New Materials, Campus D2 2, D-66123 Saarbruecken Germany *Present address: Universität Stuttgart, Institut für Biomaterialien und biomolekulare Systeme, Pfaffenwaldring 57, D-70569 Stuttgart, Germany Abstract Calorimetry, thermogravimetry and mass spectrometry were used to follow the thermal decomposition of the eight amino acids G, C, D, N, E, Q, R and H between 185°C and 280°C. Endothermic heats of decomposition between 72 and 151 kJ/mol are needed to form 12 to 70 % volatile products. This process is neither melting nor sublimation. With exception of cysteine they emit mainly H2O, some NH3 and no CO2. Cysteine produces CO2 and little else. The reactions are described by polynomials, AA → a (NH3) + b (H2O) + c (CO2) + d (H2S) + e (residue), with integer or half integer coefficients. The solid monomolecular residues are rich in peptide bonds. 1. Motivation Amino acids might have been synthesized under prebiological conditions on earth or deposited on earth from interstellar space, where they have been found [Follmann and Brownson, 2009]. Robustness of amino acids against extreme conditions is required for early occurrence, but little is known about their nonbiological thermal destruction. There is hope that one might learn something about the molecules needed in synthesis from the products found in decomposition.
    [Show full text]
  • Analysis of the Effects of Three Commercially Available Supplements on Performance, Exercise Induced Changes and Bio-Markers in Recreationally Trained Young Males
    Analysis of the effects of three commercially available supplements on performance, exercise induced changes and bio-markers in recreationally trained young males Robert Cooper A thesis is submitted in partial fulfilment of the requirements of the University of Greenwich for the Degree of Doctor of Philosophy This research programme was carried out in collaboration with GlaxoSmithKline Maxinutrition division December 2013 School of Science University of Greenwich, Medway Campus Chatham Maritime, Kent ME4 4TB, UK i DECLARATION “I certify that this work has not been accepted in substance for any degree, and is not concurrently being submitted for any degree other than that of Doctor of Philosophy being studied at the University of Greenwich. I also declare that this work is the result of my own investigations except where otherwise identified by references and that I have not plagiarised the work of others”. Signed Date Mr Robert Cooper (Candidate) …………………………………………………………………………………………………………………………… PhD Supervisors Signed Date Dr Fernando Naclerio (1st supervisor) Signed Date Dr Mark Goss-Sampson (2nd supervisor) ii ACKNOWLEDGEMENTS Thank you to my supervisory team, Dr Fernando Naclerio, Dr Mark Goss Sampson and Dr Judith Allgrove for their support and guidance throughout my PhD. Particular thanks to Dr Fernando Naclerio for his tireless efforts, guidance and support in developing the research and my own research and communication skills. Thank you to Dr Eneko Larumbe Zabala for the statistics support. I would like to take this opportunity to thank my wonderful mother and sister who continue to give me the support and drive to succeed. Also on a personal level thank you to my amazing fiancée, Jennie Swift.
    [Show full text]
  • 1 Isolation and Characterization of Cyclotides from Brazilian Psychotria
    Isolation and Characterization of Cyclotides from Brazilian Psychotria: Significance in Plant Defense and Co-occurrence with Antioxidant Alkaloids Hélio N. Matsuura,† Aaron G. Poth,‡ Anna C. A. Yendo,† Arthur G. Fett-Neto,† and David J. Craik‡,* †Center for Biotechnology and Department of Botany, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil ‡Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, Australia. 1 ABSTRACT Plants from the genus Psychotria include species bearing cyclotides and/or alkaloids. The elucidation of factors affecting the metabolism of these molecules as well as their activities may help to understand their ecological function. In the present study, high concentrations of antioxidant indole alkaloids were found to co-occur with cyclotides in Psychotria leiocarpa and P. brachyceras. The concentrations of the major cyclotides and alkaloids in P. leiocarpa and P. brachyceras were monitored following herbivore- and pathogen-associated challenges, revealing a constitutive, phytoanticipin-like accumulation pattern. Psyleio A, the most abundant cyclotide found in the leaves of P. leiocarpa, and also found in P. brachyceras leaves, exhibited insecticidal activity against Helicoverpa armigera larvae. Addition of ethanol in the vehicle for peptide solubilization in larval feeding trials proved deleterious to insecticidal activity, and resulted in increased rates of larval survival in treatments containing indole alkaloids. This suggests that plant alkaloids ingested by larvae might contribute to herbivore oxidative stress detoxification, corroborating, in a heterologous system with artificial oxidative stress stimulation, the antioxidant efficiency of Psychotria alkaloids previously observed in planta. Overall, the present study reports data for eight novel cyclotides, the identification of P.
    [Show full text]
  • The Alkaloid Emetine As a Promising Agent for the Induction and Enhancement of Drug-Induced Apoptosis in Leukemia Cells
    737-744 26/7/07 08:26 Page 737 ONCOLOGY REPORTS 18: 737-744, 2007 737 The alkaloid emetine as a promising agent for the induction and enhancement of drug-induced apoptosis in leukemia cells MAREN MÖLLER1, KERSTIN HERZER3, TILL WENGER2,4, INGRID HERR2 and MICHAEL WINK1 1Institute of Pharmacy and Molecular Biotechnology, University of Heidelberg, Im Neuenheimer Feld 364; 2Molecular OncoSurgery, Department of Surgery, University and German Cancer Research Center, Im Neuenheimer Feld 365, 69120 Heidelberg; 31st Department of Internal Medicine, University of Mainz, Langenbeckstrasse 1, 55131 Mainz, Germany; 4Centre d'Immunologie de Marseille-Luminy, Marseille, France Received January 8, 2007; Accepted February 20, 2007 Abstract. Emetine, a natural alkaloid from Psychotria caused mainly by two isoquinoline alkaloids, emetine and ipecacuanha, has been used in phytomedicine to induce cephaeline, having identical effects regarding the irritation of vomiting, and to treat cough and severe amoebiasis. Certain the respiratory tract (1). Nowadays, ipecac syrup is no longer data suggest the induction of apoptosis by emetine in recommended for the routine use in the management of leukemia cells. Therefore, we examined the suitability of poisoned patients (2) and recently a guideline on the use of emetine for the sensitisation of leukemia cells to apoptosis ipecac syrup was published, stating that ‘the circumstances in induced by cisplatin. In response to emetine, we found a which ipecac-induced emesis is the appropriate or desired strong reduction in viability, an induction of apoptosis and method of gastric decontamination are rare’ (3). Moreover, at caspase activity comparable to the cytotoxic effect of present there is a demand to remove ipecac from the over- cisplatin.
    [Show full text]
  • Effects of Dietary Methionine and Cysteine Restriction on Plasma Biomarkers, Serum Fibroblast Growth Factor 21, and Adipose Tiss
    Olsen et al. J Transl Med (2020) 18:122 https://doi.org/10.1186/s12967-020-02288-x Journal of Translational Medicine RESEARCH Open Access Efects of dietary methionine and cysteine restriction on plasma biomarkers, serum fbroblast growth factor 21, and adipose tissue gene expression in women with overweight or obesity: a double-blind randomized controlled pilot study Thomas Olsen1*, Bente Øvrebø1, Nadia Haj‑Yasein1, Sindre Lee1, Karianne Svendsen1,2, Marit Hjorth1, Nasser E. Bastani1, Frode Norheim1, Christian A. Drevon1, Helga Refsum1 and Kathrine J. Vinknes1 Abstract Background: Dietary restriction of methionine and cysteine is a well‑described model that improves metabolic health in rodents. To investigate the translational potential in humans, we evaluated the efects of dietary methio‑ nine and cysteine restriction on cardiometabolic risk factors, plasma and urinary amino acid profle, serum fbroblast growth factor 21 (FGF21), and subcutaneous adipose tissue gene expression in women with overweight and obesity in a double‑blind randomized controlled pilot study. Methods: Twenty women with overweight or obesity were allocated to a diet low (Met/Cys n 7), medium (Met/ ‑low, = Cys‑medium, n 7) or high (Met/Cys‑high, n 6) in methionine and cysteine for 7 days. The diets difered only by methio‑ nine and cysteine= content. Blood and urine= were collected at day 0, 1, 3 and 7 and subcutaneous adipose tissue biopsies were taken at day 0 and 7. Results: Plasma methionine and cystathionine and urinary total cysteine decreased, whereas FGF21 increased in the Met/Cys‑low vs. Met/Cys‑high group. The Met/Cys‑low group had increased mRNA expression of lipogenic genes in adipose tissue including DGAT1.
    [Show full text]
  • Amino Acid Requirements for Cleavage of the Rabbit Ovum
    AMINO ACID REQUIREMENTS FOR CLEAVAGE OF THE RABBIT OVUM JOSEPH C. DANIEL, Jr and JOHN D. OLSON Institute for Developmental Biology, University of Colorado, Boulder, Colorado [Received 28th October 1967) Summary. The amino acids essential for cleavage of the rabbit ovum were determined by appraisal of the growth of eggs in vitro in defined medium deficient in specific amino acids. The first cleavage will occur in amino acid-free medium but the second requires cysteine, trypto- phane, phenylalanine, lysine, arginine, and valine. Subsequent cleavage to the morula stage requires the addition of methionine, threonine and glutamine. The amino acid requirements for pre-implantation stages of the mouse have been studied by methods that permit the growth of these embryos in vitro (Whitten, 1956, 1957; Brinster, 1965; Brinster & Thomson, 1966; Gwatkin, 1966). The only comparable study that has been done with rabbit embryos has been on the 5-day blastocyst stage (Daniel & Krishnan, 1968). The purpose of this communication is to describe the results of studies designed to identify those amino acids which are essential for early cleavage of the rabbit ovum. Fertilized ova were flushed from the oviducts with Saline F (Ham & Puck, 1962) at 18 hr p.c. The eggs were cultured for 30 hr in defined culture medium FIO (Ham, 1963) with specific amino acids deleted. Media lacking groups of five amino acids were used initially to facilitate the screening; then individual amino acids from groups which did not allow normal development were screened. Controls were run in each experiment with embryos cultured in complete FIO medium and in FIO free of amino acids.
    [Show full text]
  • Therapeutic Potential of N-Acetyl Cysteine (NAC) in Preventing Cytokine Storm in COVID-19: Review of Current Evidence
    European Review for Medical and Pharmacological Sciences 2021; 25: 2802-2807 Therapeutic potential of N-acetyl cysteine (NAC) in preventing cytokine storm in COVID-19: review of current evidence R.R. MOHANTY, B.M. PADHY, S. DAS, B.R. MEHER 1Medicine All India Institute of Medical Sciences, Bhubaneswar, Odisha, India 2Pharmacology IMS & SUM Hospital, Bhubaneswar, Odisha, India Abstract. – Since November 2019, SARS death is mostly acute respiratory distress syn- 2 Coronavirus 2 disease (COVID-19) pandemic has drome (ARDS) . There are data suggesting the spread through more than 195 nations world- role of excessive immune activation and cytokine wide. Though the coronavirus infection affects storm as the cause of lung injury in COVID-193,4. all age and sex groups, the mortality is skewed The excessive immune activation and cytokine towards the elderly population and the cause storm usually occurs due to an imbalance in of death is mostly acute respiratory distress 5 syndrome (ARDS). There are data suggesting redox homeostasis of the individuals . Important the role of excessive immune activation and factors responsible for an imbalance in redox cytokine storm as the cause of lung injury in homeostasis are prolonged oxidative stress in COVID-19. The excessive immune activation and inflammation, increased reactive oxygen species cytokine storm usually occurs due to an im- (ROS) production, and decrease in glutathione balance in redox homeostasis of the individu- level6. Many antioxidants like Zinc, Vitamin C, als. Considering the antioxidant and free radical and NAC are being explored individually or in scavenging action of N acetyl cysteine (NAC), its use might be useful in COVID-19 patients by de- combination as a therapeutic agent in the man- 7 creasing the cytokine storm consequently de- agement of COVID-19 worldwide .
    [Show full text]
  • Serum Metabolite Profiles As Potential Biochemical Markers in Young
    www.nature.com/scientificreports OPEN Serum metabolite profles as potential biochemical markers in young adults with community- acquired pneumonia cured by moxifoxacin therapy Bo Zhou1, Bowen Lou2,4, Junhui Liu3* & Jianqing She2,4* Despite the utilization of various biochemical markers and probability calculation algorithms based on clinical studies of community-acquired pneumonia (CAP), more specifc and practical biochemical markers remain to be found for improved diagnosis and prognosis. In this study, we aimed to detect the alteration of metabolite profles, explore the correlation between serum metabolites and infammatory markers, and seek potential biomarkers for young adults with CAP. 13 Eligible young mild CAP patients between the ages of 18 and 30 years old with CURB65 = 0 admitted to the respiratory medical department were enrolled, along with 36 healthy participants as control. Untargeted metabolomics profling was performed and metabolites including alcohols, amino acids, carbohydrates, fatty acids, etc. were detected. A total of 227 serum metabolites were detected. L-Alanine, 2-Hydroxybutyric acid, Methylcysteine, L-Phenylalanine, Aminoadipic acid, L-Tryptophan, Rhamnose, Palmitoleic acid, Decanoylcarnitine, 2-Hydroxy-3-methylbutyric acid and Oxoglutaric acid were found to be signifcantly altered, which were enriched mainly in propanoate and tryptophan metabolism, as well as antibiotic-associated pathways. Aminoadipic acid was found to be signifcantly correlated with CRP levels and 2-Hydroxy-3-methylbutyric acid and Palmitoleic acid with PCT levels. The top 3 metabolites of diagnostic values are 2-Hydroxybutyric acid(AUC = 0.90), Methylcysteine(AUC = 0.85), and L-Alanine(AUC = 0.84). The AUC for CRP and PCT are 0.93 and 0.91 respectively.
    [Show full text]
  • N-Acetylcysteine in the Treatment of Human Arsenic Poisoning
    J Am Board Fam Pract: first published as 10.3122/jabfm.3.4.293 on 1 October 1990. Downloaded from N-Acetylcysteine In The Treatment Of Human Arsenic Poisoning Debra S. Martin, M.D., Stephen E. Willis, M.D., and David M. Cline, M.D. Abstract: A 32-year-old man was brought to the emergency department 5 1/2 hours after ingesting a potentiaIly lethal dose (900 mg) of sodium arsenate ant poison in a suicide attempt. The patient deteriorated progressively for 27 hours. After intramuscular dimercaprol and supportive measures failed to improve his condition, he was given N-acetylcysteine intravenously. The patient showed remarkable clinical improvement during the following 24 hours and was discharged from the hospital several days later. (J Am Board Fam Pract 1990; 3:293-6.) Arsenic has been used since medieval times, known use of intravenous NAC in a patient with both as medicine and poison. Although its me­ arsenic poisoning. dicinal use has declined, arsenic can still be found as an ingredient in certain homeopathic Case Report formulas, I which are available in some health A 32-year-old man was brought to the emer­ food stores. Arsenic also is present in high con­ gency department by ambulance 5 hours after centrations in many easily obtainable ant kill­ he ingested approximately 900 mg of sodium ers, and this source is responsible for most toxic arsenate - five times the lethal doseJ,6 - in a human ingestions. 2 Other sources include in­ suicide attempt. He was lethargic but arousable secticides, herbicides, and rodenticides. Com­ by voice and answered questions appropriately.
    [Show full text]
  • Methionine and Cysteine Kinetics at Different Intakes of Methionine and Cystine in Elderly Men and Women1–3
    Methionine and cysteine kinetics at different intakes of methionine and cystine in elderly men and women1–3 Naomi K Fukagawa, Yong-Ming Yu, and Vernon R Young See corresponding editorial on page 224. Downloaded from https://academic.oup.com/ajcn/article/68/2/380/4648746 by guest on 27 September 2021 ABSTRACT Earlier nitrogen balance studies led to the con- requirement for methionine. On the other hand, recent kinetic clusion that requirements for methionine in older individuals are studies by Fereday et al (6) imply that the protein requirements much higher than those in younger adults. Hence, we examined of healthy elderly, at least as assessed from tracer leucine bal- the kinetics of whole-body methionine, cysteine, and leucine ance studies, may not be any higher than those of younger adults. metabolism postabsorptively using a continuous intravenous Indeed, there is a great deal of uncertainty about the protein and 2 13 2 infusion of L-[C H3,1- C]methionine, L-[ H3]leucine, and [3,3- amino acid requirements of elderly subjects and the effects of 2 H2]cysteine in 12 elderly men (n = 5) and women (n = 7) given aging (7–9); therefore, further relevant studies in this age group as a 3-h infusion after a 12-h fast (study 1) and in 8 elderly men are highly desirable. In a review published previously (8), we (n = 4) and women (n = 4) as an 8-h infusion according to a 3-h concluded that amino acid requirements are similar in healthy fasted, 5-h fed protocol (study 2) for 6 d.
    [Show full text]
  • Cysteine, Glutathione, and Thiol Redox Balance in Astrocytes
    antioxidants Review Cysteine, Glutathione, and Thiol Redox Balance in Astrocytes Gethin J. McBean School of Biomolecular and Biomedical Science, Conway Institute, University College Dublin, Dublin, Ireland; [email protected]; Tel.: +353-1-716-6770 Received: 13 July 2017; Accepted: 1 August 2017; Published: 3 August 2017 Abstract: This review discusses the current understanding of cysteine and glutathione redox balance in astrocytes. Particular emphasis is placed on the impact of oxidative stress and astrocyte activation on pathways that provide cysteine as a precursor for glutathione. The effect of the disruption of thiol-containing amino acid metabolism on the antioxidant capacity of astrocytes is also discussed. − Keywords: cysteine; cystine; cysteamine; cystathionine; glutathione; xc cystine-glutamate exchanger; transsulfuration 1. Introduction Thiol groups, whether contained within small molecules, peptides, or proteins, are highly reactive and prone to spontaneous oxidation. Free cysteine readily oxidises to its corresponding disulfide, cystine, that together form the cysteine/cystine redox couple. Similarly, the tripeptide glutathione (γ-glutamyl-cysteinyl-glycine) exists in both reduced (GSH) and oxidised (glutathione disulfide; GSSG) forms, depending on the oxidation state of the sulfur atom on the cysteine residue. In the case of proteins, the free sulfhydryl group on cysteines can adopt a number of oxidation states, ranging from disulfides (–S–S–) and sulfenic acids (–SOOH), which are reversible, to the more oxidised sulfinic (–SOO2H) and sulfonic acids (–SOO3H), which are not. These latter species may arise as a result of chronic and/or severe oxidative stress, and generally indicate a loss of function of irreversibly oxidised proteins. Methionine residues oxidise to the corresponding sulfoxide, which can be rescued enzymatically by methionine sulfoxide reductase [1].
    [Show full text]
  • Site-Directed Mutagenesis of Cysteine to Serine in the DNA Binding Region of Nrf2 Decreases Its Capacity to Upregulate Antioxida
    Oncogene (2002) 21, 2191 ± 2200 ã 2002 Nature Publishing Group All rights reserved 0950 ± 9232/02 $25.00 www.nature.com/onc Site-directed mutagenesis of cysteine to serine in the DNA binding region of Nrf2 decreases its capacity to upregulate antioxidant response element-mediated expression and antioxidant induction of NAD(P)H:quinone oxidoreductase1 gene David Bloom1, Saravanakumar Dhakshinamoorthy1 and Anil K Jaiswal*,1 1Department of Pharmacology, Baylor College of Medicine, One Baylor Plaza, Houston, Texas, TX 77030, USA NF-E2 related factor 2 (Nrf2) is a CNC/b-zip protein mation (Thelen et al., 1993), ionizing radiation (Breen that regulates antioxidant response element (ARE)- and Murphy, 1995), and cellular respiration (Grisham mediated expression, and antioxidant induction, of and McCord, 1986). These stimuli result in the detoxifying enzyme genes, including NAD(P)H:quinone production of free radicals, including reactive oxygen oxidoreductase1 (NQO1). A comparison of Nrf2 from species (ROS). ROS, and xenobiotic and antioxidant dierent species, and with other b-zip proteins, revealed generated electrophiles, attack DNA and other cellular the presence of a highly conserved cysteine residue at macromolecules, causing aging, neurodegenerative dis- position 506 in the DNA binding domain of Nrf2. Site- eases, arthritis, arteriosclerosis, and tumor induction directed mutagenesis was used to mutate this cysteine to and promotion (Breen and Murphy, 1995; Grisham serine. Transfection/over expression experiments in hu- and McCord, 1986; Ward, 1994; Rosen et al., 1995). man hepatoblastoma (Hep-G2) cells demonstrated that Cells have developed a defense mechanism to detoxify mutant Nrf2 (mNrf2), containing the C506S mutation, and remove electrophiles and ROS.
    [Show full text]