DOCSLIB.ORG

Uva-DARE (Digital Academic Repository)

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Uva-DARE (Digital Academic Repository) UvA-DARE (Digital Academic Repository) Implications of arginine deficiency for growth and organ maturation. Studies on hair, muscle, brain and lymphoid organ maturation de Jonge, W.J. Publication date 2001 Link to publication Citation for published version (APA): de Jonge, W. J. (2001). Implications of arginine deficiency for growth and organ maturation. Studies on hair, muscle, brain and lymphoid organ maturation. General rights It is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), other than for strictly personal, individual use, unless the work is under an open content license (like Creative Commons). Disclaimer/Complaints regulations If you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library: https://uba.uva.nl/en/contact, or a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible. UvA-DARE is a service provided by the library of the University of Amsterdam (https://dare.uva.nl) Download date:05 Oct 2021 ChapterChapter I ArginineArginine biosynthesis and metabolism WouterWouter J de Jonge, Maaike J Bruins, 2Nicolaas E Deutz,2Peter B Soeters, 11 Wouter H hamers 'Departmentt of Anatomy and Embryology,3 Department of Biochemistry, Academicc Medical Center, Meibergdreef 15, 1105 AZ Amsterdam, department of Surgery,, Maastricht University (AZL), The Netherlands. 5 5 ChapterChapter I Contents: Contents: 1-Biosynthesiss of argin in e 9 1.11 Intestinal citrulline biosynthesis 1.22 Arginine biosynthesis 1.33 Hepatic arginine metabolism 1.44 Ontogeny of arginine metabolism 2-Dietaryy demand of arginine 16 2.11 Dispensable and indispensable amino acids 2.22 the homeostasis of creatine reflects a delicate arginine balance 2.33 Arginine demands in growing mammals 2.42.4 Species differences in arginine requirement and biosynthesis 3-Inbornn errors of metabolism leading to congenital arginine deficiency 19 3.11 ornithine aminotransferase 3.22 ornithine transcarbamoylase 3.33 argininosuccinate synthetase 4-Metabolismm of arginine 4.11 Intestinal utilization and catabolism of glutamine and arginine 22 4.22 Arginase I and II 4.33 Agmatine 4.44 Proline 4.55 Poly amines 4.66 Nitric oxide 5-- Regulation of metabolism by arginine 28 5.11 Effect of arginine on protein synthesis and degradation 5.22 Endocrine activity arginine 6 6 6-Guanidinoo compounds 6.11 The ornithine guanidine bi-cycle 6.22 Guanidino compounds formed after transamidination 6.33 Formation of GSA by reactive oxygen species 6.44 Pathological effects 7-Argininee transporters 7.11 Amino acid transporters 7.22 System y + 7.33 Regulation of arginine transporters 8-Argininee as an immunonutrient 8.11 Arginine and immune function 8.22 Possible mechanisms of action 9-Scopee of the thesis ChapterChapter I AbbreviationsAbbreviations and enzymes with enzyme codes used'. A-I I [ECC 3.5.3.1] :: hepatic arginase A-n n [ECC 3.5.3.1] :: kidney-type arginase AGAT T [ECC 2.1.4.1] :: arginine:glycine amidinotransferase AAT T [ECC 2.6.1.1.] :: aspartate aminotransferase ASL L [ECC 4.3.2.1] :: argininosuccinate lyase ASS S [ECC 6.3.4.5] :: argininosuccinate synthetase CPS S [ECC 6.3.4.16] :: carbamoylphosphate synthetase GMT T [ECC 2.1.1.2] :: s-adenosylmethionine:guanidinoacetate methyltransferase e OAT T [ECC 2.6.1.13] :: ornithine aminotransferase ODC C [ECC 4.1.1.17] :: ornithine decarboxylase OTC C [ECC 2.1.3.3] :: ornithine transcarbamoylase P5C C [ECC n.a.] :: pyrroline-5-carboxylate synthetase PDG G [ECC 3.5.1.2.] :: phosphate-dependent glutaminase PO O [ECC n.a.] :: proline oxidase SI I [ECC 3.2.1.48- ECC = enzyme code, n.a.= not assigned Introduction Introduction 1-Biosynthesis1-Biosynthesis ofarginine 1.1-Intestinal1.1-Intestinal citrulline biosynthesis Thee organ perfusion studies by Windmueller and Spaeth *'2 established that de novo synthesiss of citrulline, as well as ornithine and proline, takes place in the small intestinee (Fig. 1). Citrulline synthesis requires NH3, CO2, and ornithine. The NH3 is derivedd from glutamine via the action of glutaminase. Together with bicarbonate, NH33 can form carbamoylphosphate by the action of carbamoylphosphate synthetase (CPS-1;; EC 6.3.4.16), an enzyme that requires N-acetylglutamate for activity. The carbamoyll group is transferred to ornithine to form citrulline in a reaction catalyzedd by ornithine transcarbamoylase (OTC; EC 2.1.3.3). In addition to glutamate,, proline can function as a precursor for the intestinal ornithine synthesis (Fig.. 1) 3, via the formation of P5C by proline oxidase, and the subsequent non- enzymaticc conversion into L-glutamyl-y-semialdehyde 4. Thee enzymes involved in citrulline synthesis, phosphate-dependent glutaminase,, OAT, and aspartate aminotransferase are found in a variety of tissues 55''66,, but CPS I, OTC, and N-acetyl glutamate synthetase expression are restricted to thee liver and intestinal mucosa 7. P5C synthetase, which catalyzes the multistep conversionn of glutamate via glutamyl-y-semialdehyde into P5C 4, is present almost exclusivelyy in the small intestinal mucosa, with only trace amounts in other tissues 4.. P5C is, in turn, converted into ornithine by OAT. For this reason, the intestine is thee only organ that has the capacity of net production of ornithine. In (most) other organs,, including liver, OAT converts ornithine into glutamate. Human patients sufferingg from a deficiency in P5C synthetase develop hyperammonemia and hypoornithinemiaa 8. In addition, these patients have decreased proline levels, implyingg that P5C-S may also have a P5C-R like activity. The essential role of the intestinee to provide citrulline for arginine biosynthesis elsewhere, is also demonstratedd by the arginine deficiency that results from inhibition of intestinal 9 9 ChapterChapter I citrullinee synthesis, as a result of inhibition or deficiency of OTC ' , OAT ' , or byy massive resection of the small bowel . Inn intestinal tissue, arterial and luminal glutamine is the main metabolicc contributor of intestinal citrulline biosynthesis 2. The magnitude of the rolee of proline in citrulline synthesis is disputed. In pigs, there is no arterial uptake off proline by the gut 14, suggesting that only dietary proline is metabolized into citrulline.. Indeed, a prominent role for proline is suggested by the observation that, att least in pigs, proline is among the most abundant amino acids in the sow's milk 14 4 protein n<4 ~ ~ Glutamine e - purines 11 -glutaminase 10-AAT 10-AAT CX-KGG <4r Glutamate e asparanginn oxaloacetate 2-P5C-S2-P5C-S NHj ATp^ C02 9-PO 9-PO proline e - P5C A— Glu-sem m 4-CPS 4-CPS \\ 3-OAT W W CP P OrnVV 5-OTC urea a if f ornithine e Cit t cycle e 7-ASL7-ASL 6-ASS —— AS Fig.. 1: Scheme of the relation between glutamine and the ornithine cycle. Enzymes that catalyze the reactionss are: 1- phosphate-dependent glutaminase [EC 3.5.1.2.], 2- pyrroline-5-carboxylate synthetase [EC n.a.],, 3- ornithine aminotransferase [EC 2.6.1.13], 4- carbamoyl-phosphate synthetase [EC 6.3.4.16], 5- ornithinee transcarbamoylase [EC 2.1.3.3], 6- argininosuccinate synthetase [EC 6.3.4.5], 7- argininosuccinate lyasee [EC 4.3.2.1], 8- hepatic arginase [EC 3.5.3.1]/ - kidney-type arginase [EC 3.5.3.1], 9- proline oxidase [EC n.a.].. 10- aspartate aminotransferase [EC 2.6.1.1]. Enzymes 6, 7 and 8 are cytosolic, 1-5 and 9 are mitochondrial,, and enzyme 10 is both cytosolic and mitochondrial. Thoughh proline oxidase (PO) is reported to be present mainly in liver and kidney 6'15,, other groups have detected a relatively high level of PO activity in the intestinal 10 0 Introduction Introduction mucosaa of pig and rat16'17. This difference has been attributed to instability of the enzymee during homogenization of, specifically, mucosal tissue6. 1.2-A1.2-A rgin ine biosyn thesis 1.2.1-Renal1.2.1-Renal arginine biosynthesis. InIn the adult kidney, arginine is made endogenously by converting citrulline into arginine,, mainly in the renal proximal tubules l'18, via the cytosolic enzymes ASS andd ASL. The kidney accounts for 60 % of arginine synthesis from circulating citrullinee 19 (see section 2.2.2). Although the kidney expresses CPS-I, (unpublished observation),, as well as glutaminase and glutamate dehydrogenase (GDH)20'21 in the preweaningg period, the adult kidney lacks the capacity for carbamoylphosphate synthesis. Thee citrulline that is metabolized into arginine by the kidneys derives primarilyy from the intestine x'21. The amount of citrulline taken up for arginine synthesiss has been shown to be proportional to the amount released by the intestine U3.. Furthermore, a positive correlation between renal citrulline uptake and arginine productionn has been shown in humans 24, sheep 25 and rats 26. The capacity of the kidneyy to synthesize arginine exceeds the capacity of the intestine to synthesize citrullinee several-fold, indicating that renal arginine synthesis depends on intestinal citrullinee synthesis 2?. In addition, the renal arginine flux is highly regulated: renal ASSS and ASL mRNA as well as activity are upregulated during a high protein diet28, 29 9 uponn starvation , or upon an acute decrease in circulating arginine levels under pathologicall conditions30. Nextt to the cytosolic arginine-synthesizing enzymes, the kidney expresses A-III (EC 3.5.3.1)31, but the expression of arginase, ASS and ASL is segregated in differentt parts of the nephron, arginine synthesis is restricted to the upstream portionss of proximal convoluted tubules, whereas arginase activity is present mainly inn the cortical and outer medullary portions of straight proximal tubules.
Load more

Recommended publications
  • The Janus-Like Role of Proline Metabolism in Cancer Lynsey Burke1,Innaguterman1, Raquel Palacios Gallego1, Robert G
    Burke et al. Cell Death Discovery (2020) 6:104 https://doi.org/10.1038/s41420-020-00341-8 Cell Death Discovery REVIEW ARTICLE Open Access The Janus-like role of proline metabolism in cancer Lynsey Burke1,InnaGuterman1, Raquel Palacios Gallego1, Robert G. Britton1, Daniel Burschowsky2, Cristina Tufarelli1 and Alessandro Rufini1 Abstract The metabolism of the non-essential amino acid L-proline is emerging as a key pathway in the metabolic rewiring that sustains cancer cells proliferation, survival and metastatic spread. Pyrroline-5-carboxylate reductase (PYCR) and proline dehydrogenase (PRODH) enzymes, which catalyze the last step in proline biosynthesis and the first step of its catabolism, respectively, have been extensively associated with the progression of several malignancies, and have been exposed as potential targets for anticancer drug development. As investigations into the links between proline metabolism and cancer accumulate, the complexity, and sometimes contradictory nature of this interaction emerge. It is clear that the role of proline metabolism enzymes in cancer depends on tumor type, with different cancers and cancer-related phenotypes displaying different dependencies on these enzymes. Unexpectedly, the outcome of rewiring proline metabolism also differs between conditions of nutrient and oxygen limitation. Here, we provide a comprehensive review of proline metabolism in cancer; we collate the experimental evidence that links proline metabolism with the different aspects of cancer progression and critically discuss the potential mechanisms involved. ● How is the rewiring of proline metabolism regulated Facts depending on cancer type and cancer subtype? 1234567890():,; 1234567890():,; 1234567890():,; 1234567890():,; ● Is it possible to develop successful pharmacological ● Proline metabolism is widely rewired during cancer inhibitor of proline metabolism enzymes for development.
    [Show full text]
  • Amino Acid Disorders 105
    AMINO ACID DISORDERS 105 Massaro, A. S. (1995). Trypanosomiasis. In Guide to Clinical tions in biological fluids relatively easy. These Neurology (J. P. Mohrand and J. C. Gautier, Eds.), pp. 663– analyzers separate amino acids either by ion-ex- 667. Churchill Livingstone, New York. Nussenzweig, V., Sonntag, R., Biancalana, A., et al. (1953). Ac¸a˜o change chromatography or by high-pressure liquid de corantes tri-fenil-metaˆnicos sobre o Trypanosoma cruzi in chromatography. The results are plotted as a graph vitro: Emprego da violeta de genciana na profilaxia da (Fig. 1). The concentration of each amino acid can transmissa˜o da mole´stia de chagas por transfusa˜o de sangue. then be calculated from the size of the corresponding O Hospital (Rio de Janeiro) 44, 731–744. peak on the graph. Pagano, M. A., Segura, M. J., DiLorenzo, G. A., et al. (1999). Cerebral tumor-like American trypanosomiasis in Most amino acid disorders can be diagnosed by acquired immunodeficiency syndrome. Ann. Neurol. 45, measuring the concentrations of amino acids in 403–406. blood plasma; however, some disorders of amino Rassi, A., Trancesi, J., and Tranchesi, B. (1982). Doenc¸ade acid transport are more easily recognized through the Chagas. In Doenc¸as Infecciosas e Parasita´rias (R. Veroesi, Ed.), analysis of urine amino acids. Therefore, screening 7th ed., pp. 674–712. Guanabara Koogan, Sa˜o Paulo, Brazil. Spina-Franc¸a, A., and Mattosinho-Franc¸a, L. C. (1988). for amino acid disorders is best done using both South American trypanosomiasis (Chagas’ disease). In blood and urine specimens. Occasionally, analysis of Handbook of Clinical Neurology (P.
    [Show full text]
  • Yeast Genome Gazetteer P35-65
    gazetteer Metabolism 35 tRNA modification mitochondrial transport amino-acid metabolism other tRNA-transcription activities vesicular transport (Golgi network, etc.) nitrogen and sulphur metabolism mRNA synthesis peroxisomal transport nucleotide metabolism mRNA processing (splicing) vacuolar transport phosphate metabolism mRNA processing (5’-end, 3’-end processing extracellular transport carbohydrate metabolism and mRNA degradation) cellular import lipid, fatty-acid and sterol metabolism other mRNA-transcription activities other intracellular-transport activities biosynthesis of vitamins, cofactors and RNA transport prosthetic groups other transcription activities Cellular organization and biogenesis 54 ionic homeostasis organization and biogenesis of cell wall and Protein synthesis 48 plasma membrane Energy 40 ribosomal proteins organization and biogenesis of glycolysis translation (initiation,elongation and cytoskeleton gluconeogenesis termination) organization and biogenesis of endoplasmic pentose-phosphate pathway translational control reticulum and Golgi tricarboxylic-acid pathway tRNA synthetases organization and biogenesis of chromosome respiration other protein-synthesis activities structure fermentation mitochondrial organization and biogenesis metabolism of energy reserves (glycogen Protein destination 49 peroxisomal organization and biogenesis and trehalose) protein folding and stabilization endosomal organization and biogenesis other energy-generation activities protein targeting, sorting and translocation vacuolar and lysosomal
    [Show full text]
  • 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.
    [Show full text]
  • Low Proline Diet in Type I Hyperprolinaemia
    Arch Dis Child: first published as 10.1136/adc.46.245.72 on 1 February 1971. Downloaded from Archives of Disease in Childhood, 1971, 46, 72. Low Proline Diet in Type I Hyperprolinaemia J. T. HARRIES, A. T. PIESOWICZ,* J. W. T. SEAKINS, D. E. M. FRANCIS, and 0. H. WOLFF From The Hospital for Sick Children, and the Institute of Child Health, University of London Harries, J. T., Piesowicz, A. T., Seakins, J. W. T., Francis, D. E. M., and Wolff, 0. H. (1971). Archives of Disease in Childhood, 46, 72. Low proline diet in type I hyperprolinaemia. A diagnosis of Type I hyperprolinaemia was made in a 7-month-old infant who presented with hypocalcaemic convulsions and malabsorp- tion. The plasma levels of proline were grossly raised and the urinary excretion of proline, hydroxyproline, and glycine was increased; neurological development was delayed and there were associated abnormalities of the electroencephalogram, renal tract, and bones. Restriction of dietary proline at the age of 9 months resulted in a prompt fall of plasma levels of proline to normal, and a low proline diet was continued until the age of 27 months when persistence of the biochemical defect was shown. During the period of dietary treatment, growth was satisfactory, mental development improved, and the electroencephalogram, and the renal, skeletal, and intestinal abnormalities disappeared. Proline should be regarded as a 'semi-essential' amino acid in the growing infant. Hyperprolinaemia, appearing in several members balance can be maintained on a proline-free diet copyright. of a family was first described by Scriver, Schafer, (Rose et al., 1955), and therefore the amino acid is and Efron in 1961.
    [Show full text]
  • Proline Metabolism in Glucagon Treated Rats
    PROLINE CATABOLISM IN LIVER by © Michael Roland Haslett A thesis submitted to the School of Graduate Studies in partial fulfilment of the requirements for the degree of Master of Science Department of Biochemistry Memorial University of Newfoundland and Labrador 2009 St. John's Newfoundland and Labrador, Canada Abstract The goal of this work was to localize one of the enzymes involved in proline oxidation, 111-pyrroline-5-carboxylate dehydrogenase (P5CDh) and to gain an understanding of the factors affecting proline catabolism in rat liver. In this regard we performed a systematic subcellular localization for P5CDh and studied proline catabolism in response to dietary protein and exogenous glucagon. Our results indicate that P5CDh is located solely in mitochondria in rat liver. With respect to factors affecting proline catabolism we observed that rats fed a diet containing excess protein (45% casein) display a 1.5 fold increase in activity of P5CDh and proline oxidase (PO), and a 40% increase in flux through the pathway resulting in complete oxidation of proline in isolated mitochondria. We also observed that rats administered exogenous glucagon exhibit a 2 fold increase in PO activity and a 1.5 fold increase in P5CDh activity, and a 2 fold increase in flux through the pathway resulting in complete oxidation of proline in 14 14 isolated mitochondria. C02 production from C-proline in the isolated nonrecirculating perfused rat liver was also elevated 2 fold in the glucagon treated rat. We also studied the transport of proline into isolated hepatocytes and observed a 1.5 fold increase in the transport of proline in rats given exogenous glucagon.
    [Show full text]
  • (12) Patent Application Publication (10) Pub. No.: US 2003/0082511 A1 Brown Et Al
    US 20030082511A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2003/0082511 A1 Brown et al. (43) Pub. Date: May 1, 2003 (54) IDENTIFICATION OF MODULATORY Publication Classification MOLECULES USING INDUCIBLE PROMOTERS (51) Int. Cl." ............................... C12O 1/00; C12O 1/68 (52) U.S. Cl. ..................................................... 435/4; 435/6 (76) Inventors: Steven J. Brown, San Diego, CA (US); Damien J. Dunnington, San Diego, CA (US); Imran Clark, San Diego, CA (57) ABSTRACT (US) Correspondence Address: Methods for identifying an ion channel modulator, a target David B. Waller & Associates membrane receptor modulator molecule, and other modula 5677 Oberlin Drive tory molecules are disclosed, as well as cells and vectors for Suit 214 use in those methods. A polynucleotide encoding target is San Diego, CA 92121 (US) provided in a cell under control of an inducible promoter, and candidate modulatory molecules are contacted with the (21) Appl. No.: 09/965,201 cell after induction of the promoter to ascertain whether a change in a measurable physiological parameter occurs as a (22) Filed: Sep. 25, 2001 result of the candidate modulatory molecule. Patent Application Publication May 1, 2003 Sheet 1 of 8 US 2003/0082511 A1 KCNC1 cDNA F.G. 1 Patent Application Publication May 1, 2003 Sheet 2 of 8 US 2003/0082511 A1 49 - -9 G C EH H EH N t R M h so as se W M M MP N FIG.2 Patent Application Publication May 1, 2003 Sheet 3 of 8 US 2003/0082511 A1 FG. 3 Patent Application Publication May 1, 2003 Sheet 4 of 8 US 2003/0082511 A1 KCNC1 ITREXCHO KC 150 mM KC 2000000 so 100 mM induced Uninduced Steady state O 100 200 300 400 500 600 700 Time (seconds) FIG.
    [Show full text]
  • Proline Dehydrogenase Is Essential for Proline Protection Against
    University of Nebraska - Lincoln DigitalCommons@University of Nebraska - Lincoln Biochemistry -- Faculty Publications Biochemistry, Department of 2012 Proline dehydrogenase is essential for proline protection against hydrogen peroxide induced cell death Sathish Kumar Natarajan University of Nebraska - Lincoln, [email protected] Weidong Zhu University of Nebraska-Lincoln Xinwen Liang University of Nebraska - Lincoln, [email protected] Lu Zhang University of Nebraska-Lincoln, [email protected] Andrew Demers University of Nebraska-Lincoln, [email protected] See next page for additional authors Follow this and additional works at: http://digitalcommons.unl.edu/biochemfacpub Part of the Biochemistry Commons, Biotechnology Commons, and the Other Biochemistry, Biophysics, and Structural Biology Commons Natarajan, Sathish Kumar; Zhu, Weidong; Liang, Xinwen; Zhang, Lu; Demers, Andrew; Zimmerman, Matthew C.; Simpson, Melanie A.; and Becker, Donald F., "Proline dehydrogenase is essential for proline protection against hydrogen peroxide induced cell death" (2012). Biochemistry -- Faculty Publications. 276. http://digitalcommons.unl.edu/biochemfacpub/276 This Article is brought to you for free and open access by the Biochemistry, Department of at DigitalCommons@University of Nebraska - Lincoln. It has been accepted for inclusion in Biochemistry -- Faculty Publications by an authorized administrator of DigitalCommons@University of Nebraska - Lincoln. Authors Sathish Kumar Natarajan, Weidong Zhu, Xinwen Liang, Lu Zhang, Andrew Demers, Matthew C. Zimmerman, Melanie A. Simpson, and Donald F. Becker This article is available at DigitalCommons@University of Nebraska - Lincoln: http://digitalcommons.unl.edu/biochemfacpub/276 NIH Public Access Author Manuscript Free Radic Biol Med. Author manuscript; available in PMC 2013 September 01. NIH-PA Author ManuscriptPublished NIH-PA Author Manuscript in final edited NIH-PA Author Manuscript form as: Free Radic Biol Med.
    [Show full text]
  • Dr. Kiran Meena Department of Biochemistry Kiranmeena2104
    Dr. Kiran Meena Department of Biochemistry [email protected] Class 7-8: 1-11-2018 (2:00 to 4:00 PM) Learning Objectives Catabolism of the Carbon Skeletons of amino acids and related disorders: • Catabolism of Phenylalanine and Tyrosine with genetic disorders • Arginine, Histidine, glutamate, glutamine and proline to α-ketoglutarate • Methionine, isoleucine, threonine and valine to Succinyl CoA • Degradation of branched chain aa (Leucine to Acetoacetate and Acetyl-CoA, Valine to β- Aminoisobutyrate and Succinyl-CoA and Isoleucine to Acetyl-CoA and Propionyl-CoA) • Asparagine and Aspartate to Oxaloacetate Conversion of amino acids to Specialized products Catabolism of Phenylalanine and Tyrosine with genetic disorders Homogentisate Oxidase/ Neonatal Tyrosinemia or Or p-hydroxyphenylpyruvate hydroxylase Fig18.23: Lehninger Principles of Biochemistry by David L Nelson Disorder related to phenylalanine catabolism Phenylketonuria (PKU) • Genetic defect in phenylalanine hydroxylase, first enzyme in catabolic pathway for phenylalanine, is responsible for disease phenylketonuria (PKU),most common cause of elevated levels of phenylalanine (hyperphenylalaninemia) • Excess phenylalanine is transaminated to Phenylpyruvate • The “spillover” of Phenylpyruvate (a phenylketone) into urine • High concentration of phenylalanine itself gives rise to brain dysfunction. Cont-- • Phenylalanine hydroxylase requires the cofactor tetrahydrobiopterin, which carries electrons from NADH to O2 and becomes oxidized to dihydrobiopterin • It is subsequently reduced
    [Show full text]
  • The Microsomal Dicarboxylyl-Coa Synthetase
    Biochem. J. (1985) 230, 683-693 683 Prinited in Great Britaini The microsomal dicarboxylyl-CoA synthetase Joseph VAMECQ,* Edmond DE HOFFMANNt and Francois VAN HOOF* *Laboratoire de Chimie Physiologique, Universite Catholique de Louvain and International Institute ofCellular and Molecular Pathology, UCL 75.39, 75 Avenue Hippocrate, B-1200 Brussels, Belgium, and tUnite de Cinetique, Combustion et Chimie Organique Physique, Universite Catholique de Louvain, Batiment Lavoisier, Place L. Pasteur 1, B-1348 Louvain-la-Neuve, Belgium (Received 11 March 1985/7 May 1985; accepted 30 May 1985) Dicarboxylic acids are products of the co-oxidation of monocarboxylic acids. We demonstrate that in rat liver dicarboxylic acids (C5-C1 6) can be converted into their CoA esters by a dicarboxylyl-CoA synthetase. During this activation ATP, which cannot be replaced by GTP, is converted into AMP and PP,, both acting as feedback inhibitors of the reaction. Thermolabile at 37°C, and optimally active at pH6.5, dicarboxylyl-CoA synthetase displays the highest activity on dodecanedioic acid (2yrmol/min per g of liver). Cell-fractionation studies indicate that this enzyme belongs to the hepatic microsomal fraction. Investigations about the fate of dicarboxylyl-CoA esters disclosed the existence of an oxidase, which could be measured by monitoring the production of H202. In our assay conditions this H202 production is dependent on and closely follows the CoA consumption. It appears that the chain-length specificity of the handling of dicarboxylic acids by this catabolic pathway (activation to acyl-CoA and oxidation with H202 production) parallels the pattern of the degradation of exogenous dicarboxylic acids in vivo.
    [Show full text]
  • Antenatal Diagnosis of Inborn Errors Ofmetabolism
    816 ArchivesofDiseaseinChildhood 1991;66: 816-822 CURRENT PRACTICE Arch Dis Child: first published as 10.1136/adc.66.7_Spec_No.816 on 1 July 1991. Downloaded from Antenatal diagnosis of inborn errors of metabolism M A Cleary, J E Wraith The introduction of experimental treatment for Sample requirement and techniques used in lysosomal storage disorders and the increasing prenatal diagnosis understanding of the molecular defects behind By far the majority of antenatal diagnoses are many inborn errors have overshadowed the fact performed on samples obtained by either that for many affected families the best that can amniocentesis or chorion villus biopsy. For be offered is a rapid, accurate prenatal diag- some disorders, however, the defect is not nostic service. Many conditions remain at best detectable in this material and more invasive only partially treatable and as a consequence the methods have been applied to obtain a diagnos- majority of parents seek antenatal diagnosis in tic sample. subsequent pregnancies, particularly for those disorders resulting in a poor prognosis in terms of either life expectancy or normal neurological FETAL LIVER BIOPSY development. Fetal liver biopsy has been performed to The majority of inborn errors result from a diagnose ornithine carbamoyl transferase defi- specific enzyme deficiency, but in some the ciency and primary hyperoxaluria type 1. primary defect is in a transport system or Glucose-6-phosphatase deficiency (glycogen enzyme cofactor. In some conditions the storage disease type I) could also be detected by biochemical defect is limited to specific tissues this method. The technique, however, is inva- only and this serves to restrict the material avail- sive and can be performed by only a few highly able for antenatal diagnosis for these disorders.
    [Show full text]
  • Phytohormones Regulate Accumulation of Osmolytes Under Abiotic Stress
    biomolecules Review Phytohormones Regulate Accumulation of Osmolytes Under Abiotic Stress Anket Sharma 1,* , Babar Shahzad 2, Vinod Kumar 3 , Sukhmeen Kaur Kohli 4, Gagan Preet Singh Sidhu 5, Aditi Shreeya Bali 6, Neha Handa 7 , Dhriti Kapoor 7, Renu Bhardwaj 4 and Bingsong Zheng 1,* 1 State Key Laboratory of Subtropical Silviculture, Zhejiang A&F University, Hangzhou 311300, China 2 School of Land and Food, University of Tasmania, Hobart, Tasmania 7005, Australia 3 Department of Botany, DAV University, Sarmastpur, Jalandhar 144012, Punjab, India 4 Plant Stress Physiology Laboratory, Department of Botanical & Environmental Sciences, Guru Nanak Dev University, Amritsar 143005, India 5 Department of Environment Education, Government College of Commerce and Business Administration, Chandigarh 160047, India 6 Mehr Chand Mahajan D.A.V. College for Women, Chandigarh 160036, India 7 School of Bioengineering & Biosciences, Lovely Professional University, Phagwara 144411, India * Correspondence: [email protected] (A.S.); [email protected] (B.Z.); Tel.: +86-(0)-5716-373-0936 (B.Z.) Received: 13 June 2019; Accepted: 16 July 2019; Published: 17 July 2019 Abstract: Plants face a variety of abiotic stresses, which generate reactive oxygen species (ROS), and ultimately obstruct normal growth and development of plants. To prevent cellular damage caused by oxidative stress, plants accumulate certain compatible solutes known as osmolytes to safeguard the cellular machinery. The most common osmolytes that play crucial role in osmoregulation are proline, glycine-betaine, polyamines, and sugars. These compounds stabilize the osmotic differences between surroundings of cell and the cytosol. Besides, they also protect the plant cells from oxidative stress by inhibiting the production of harmful ROS like hydroxyl ions, superoxide ions, hydrogen peroxide, and other free radicals.
    [Show full text]