DOCSLIB.ORG
Recommended publications
  • 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.
    [Show full text]
  • Mutation of the Fumarase Gene in Two Siblings with Progressive Encephalopathy and Fumarase Deficiency T
    Mutation of the Fumarase Gene in Two Siblings with Progressive Encephalopathy and Fumarase Deficiency T. Bourgeron,* D. Chretien,* J. Poggi-Bach, S. Doonan,' D. Rabier,* P. Letouze,I A. Munnich,* A. R6tig,* P. Landneu,* and P. Rustin* *Unite de Recherches sur les Handicaps Genetiques de l'Enfant, INSERM U393, Departement de Pediatrie et Departement de Biochimie, H6pital des Enfants-Malades, 149, rue de Sevres, 75743 Paris Cedex 15, France; tDepartement de Pediatrie, Service de Neurologie et Laboratoire de Biochimie, Hopital du Kremlin-Bicetre, France; IFaculty ofScience, University ofEast-London, UK; and IService de Pediatrie, Hopital de Dreux, France Abstract chondrial enzyme (7). Human tissue fumarase is almost We report an inborn error of the tricarboxylic acid cycle, fu- equally distributed between the mitochondria, where the en- marase deficiency, in two siblings born to first cousin parents. zyme catalyzes the reversible hydration of fumarate to malate They presented with progressive encephalopathy, dystonia, as a part ofthe tricarboxylic acid cycle, and the cytosol, where it leucopenia, and neutropenia. Elevation oflactate in the cerebro- is involved in the metabolism of the fumarate released by the spinal fluid and high fumarate excretion in the urine led us to urea cycle. The two isoenzymes have quite homologous struc- investigate the activities of the respiratory chain and of the tures. In rat liver, they differ only by the acetylation of the Krebs cycle, and to finally identify fumarase deficiency in these NH2-terminal amino acid of the cytosolic form (8). In all spe- two children. The deficiency was profound and present in all cies investigated so far, the two isoenzymes have been found to tissues investigated, affecting the cytosolic and the mitochon- be encoded by a single gene (9,10).
    [Show full text]
  • 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
    [Show full text]
  • Estrogen Receptor-Mediated Neuroprotection: the Role of the Alzheimer’S Disease-Related Gene Seladin-1
    REVIEW Estrogen receptor-mediated neuroprotection: The role of the Alzheimer’s disease-related gene seladin-1 Alessandro Peri Abstract: Experimental evidence supports a protective role of estrogen in the brain. According Mario Serio to the fact that Alzheimer’s disease (AD) is more common in postmenopausal women, estrogen treatment has been proposed. However, there is no general consensus on the benefi cial effect of Department of Clinical Physiopathology, Endocrine Unit, estrogen or selective estrogen receptor modulators in preventing or treating AD. It has to be said that Center for Research, Transfer several factors may markedly affect the effi cacy of the treatment. A few years ago, the seladin-1 gene and High Education on Chronic, Inflammatory, Degenerative (for selective Alzheimer’s disease indicator-1) has been isolated and found to be down-regulated and Neoplastic Disorders in brain regions affected by AD. Seladin-1 has been found to be identical to the gene encoding the for the Development of Novel enzyme 3-beta-hydroxysterol delta-24-reductase, involved in the cholesterol biosynthetic pathway, Therapies (DENOThe), University β of Florence, Florence, Italy which confers protection against -amyloid-mediated toxicity and from oxidative stress, and is an effective inhibitor of caspase-3 activity, a key mediator of apoptosis. Interestingly, we found earlier that the expression of this gene is up-regulated by estrogen. Furthermore, our very recent data support the hypothesis that seladin-1 is a mediator of the neuroprotective effects of estrogen. This review will summarize the current knowledge regarding the neuroprotective effects of seladin-1 and the relationship between this protein and estrogen.
    [Show full text]
  • Inherited Metabolic Disorders)
    1 โรคพันธุกรรมเมตาบอลิก (inherited metabolic disorders) บทนํา โรคพันธุกรรมเมตาบอลิคนั้น มีผู้ประเมินไว้ว่ามีหลายร้อยโรคด้วยกัน และเป็นที่ยอมรับว่า อุบัติการของโรคกลุ่มนี้มักจะน้อยกว่าความเป็นจริง เนื่องจากการวินิจฉัยโรคทําได้ด้วยความ ยากลําบาก แพทย์ทั่วไปมักรู้จักค่อนข้างน้อย หรือให้การวินิจฉัยไม่ถูกต้อง ด้วยเหตุผลหลาย ประการ 1). การวินิจฉัยทําได้ค่อนข้างยาก เนื่องจากแต่ละโรคพบได้น้อยคือ จัดเป็น rare disease ทําให้แพทย์ไม่ค่อยนึกถึงเมื่อพบผู้ป่วย จนอาการค่อนข้างมาก หรือเมื่อได้แยกโรคที่พบได้บ่อย ออกไปแล้ว 2). การตรวจทางห้องปฎิบัติการโดยเฉพาะการตรวจเลือดและปัสสาวะเบื้องต้น มักไม่ ค่อยบอกโรคชัดเจน ยกเว้นส่งตรวจพิเศษบางอย่างเช่นการวิเคราะห์ plasma amino acid หรือ urine organic acid 3). ในทารกแรกเกิดซึ่งมีโอกาสพบโรคกลุ่มนี้ได้บ่อย มักจะมีการตอบสนองต่อ severe overwhelming illness อย่างมีขีดจํากัด หรือแสดงอาการอย่าง nonspecific เช่น poor feeding,lethargy เป็นต้น 4).กุมารแพทย์คิดถึงโรคกลุ่มนี้ในบางภาวะเท่านั้นเช่นภาวะปัญญาอ่อน หรือชักที่คุมได้ยากและมองข้ามอาการแสดงบางอย่างที่อาจเป็นเงื่อนงําสําคัญในการวินิจฉัยโรค โรคพันธุกรรมเมตาบอลิก ที่เรียกว่า inherited metabolic disorders หรือ inborn errors of metabolism (IBEM) เป็นโรคพันธุกรรมกลุ่มหนึ่งที่เกิดจากความผิดปกติของยีนเดี่ยว ที่มีความ ผิดปกติของการเรียงลําดับของเบสหรือสายDNA ก่อให้เกิดความผิดปกติของ enzymes, receptors, transport proteins, structural proteins, หรือส่วนประกอบอื่นของเซลล์แล้วส่งผลให้ เกิดความผิดปกติของขบวนการย่อยสลาย (catabolism) หรือขบวนการสังเคราะห์ (anabolism) สารอาหาร การเปลี่ยนแปลงที่ระดับ DNA ของโรคกลุ่มนี้อาจเกิดจากการกลายพันธุ์ของยีนที่สร้าง enzyme หรือยีนที่สร้างสารควบคุมหรือส่งเสริมการทํางานของ
    [Show full text]
  • Genes in Eyecare Geneseyedoc 3 W.M
    Genes in Eyecare geneseyedoc 3 W.M. Lyle and T.D. Williams 15 Mar 04 This information has been gathered from several sources; however, the principal source is V. A. McKusick’s Mendelian Inheritance in Man on CD-ROM. Baltimore, Johns Hopkins University Press, 1998. Other sources include McKusick’s, Mendelian Inheritance in Man. Catalogs of Human Genes and Genetic Disorders. Baltimore. Johns Hopkins University Press 1998 (12th edition). http://www.ncbi.nlm.nih.gov/Omim See also S.P.Daiger, L.S. Sullivan, and B.J.F. Rossiter Ret Net http://www.sph.uth.tmc.edu/Retnet disease.htm/. Also E.I. Traboulsi’s, Genetic Diseases of the Eye, New York, Oxford University Press, 1998. And Genetics in Primary Eyecare and Clinical Medicine by M.R. Seashore and R.S.Wappner, Appleton and Lange 1996. M. Ridley’s book Genome published in 2000 by Perennial provides additional information. Ridley estimates that we have 60,000 to 80,000 genes. See also R.M. Henig’s book The Monk in the Garden: The Lost and Found Genius of Gregor Mendel, published by Houghton Mifflin in 2001 which tells about the Father of Genetics. The 3rd edition of F. H. Roy’s book Ocular Syndromes and Systemic Diseases published by Lippincott Williams & Wilkins in 2002 facilitates differential diagnosis. Additional information is provided in D. Pavan-Langston’s Manual of Ocular Diagnosis and Therapy (5th edition) published by Lippincott Williams & Wilkins in 2002. M.A. Foote wrote Basic Human Genetics for Medical Writers in the AMWA Journal 2002;17:7-17. A compilation such as this might suggest that one gene = one disease.
    [Show full text]
  • Targeted Therapies for Metabolic Myopathies Related to Glycogen Storage and Lipid Metabolism: a Systematic Review and Steps Towards a ‘Treatabolome’
    Journal of Neuromuscular Diseases 8 (2021) 401–417 401 DOI 10.3233/JND-200621 IOS Press Systematic Review Targeted Therapies for Metabolic Myopathies Related to Glycogen Storage and Lipid Metabolism: a Systematic Review and Steps Towards a ‘Treatabolome’ A. Mantaa,b, S. Spendiffb, H. Lochmuller¨ b,c,d,e,f and R. Thompsonb,∗ aFaculty of Medicine, University of Ottawa, Ottawa, ON, Canada bChildren’s Hospital of Eastern Ontario Research Institute, Ottawa, ON, Canada cDepartment of Neuropediatrics and Muscle Disorders, Medical Center – University of Freiburg, Faculty of Medicine, Freiburg, Germany dCentro Nacional de An´alisis Gen´omico (CNAG-CRG), Center for Genomic Regulation, Barcelona Institute of Science and Technology (BIST), Barcelona, Catalonia, Spain eDivision of Neurology, Department of Medicine, The Ottawa Hospital, University of Ottawa, Ottawa, Canada f Brain and Mind Research Institute, University of Ottawa, Ottawa, Canada Abstract. Background: Metabolic myopathies are a heterogenous group of muscle diseases typically characterized by exercise intoler- ance, myalgia and progressive muscle weakness. Effective treatments for some of these diseases are available, but while our understanding of the pathogenesis of metabolic myopathies related to glycogen storage, lipid metabolism and ␤-oxidation is well established, evidence linking treatments with the precise causative genetic defect is lacking. Objective: The objective of this study was to collate all published evidence on pharmacological therapies for the aforemen- tioned metabolic myopathies and link this to the genetic mutation in a format amenable to databasing for further computational use in line with the principles of the “treatabolome” project. Methods: A systematic literature review was conducted to retrieve all levels of evidence examining the therapeutic efficacy of pharmacological treatments on metabolic myopathies related to glycogen storage and lipid metabolism.
    [Show full text]
  • 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.
    [Show full text]
  • Sialic Acid Storage Disease
    Sialic acid storage disease Description Sialic acid storage disease is an inherited disorder that primarily affects the nervous system. People with sialic acid storage disease have signs and symptoms that may vary widely in severity. This disorder is generally classified into one of three forms: infantile free sialic acid storage disease, Salla disease, and intermediate severe Salla disease. Infantile free sialic acid storage disease (ISSD) is the most severe form of this disorder. Babies with this condition have severe developmental delay, weak muscle tone ( hypotonia), and failure to gain weight and grow at the expected rate (failure to thrive). They may have unusual facial features that are often described as "coarse," seizures, bone malformations, an enlarged liver and spleen (hepatosplenomegaly), and an enlarged heart (cardiomegaly). The abdomen may be swollen due to the enlarged organs and an abnormal buildup of fluid in the abdominal cavity (ascites). Affected infants may have a condition called hydrops fetalis in which excess fluid accumulates in the body before birth. Children with this severe form of the condition usually live only into early childhood. Salla disease is a less severe form of sialic acid storage disease. Babies with Salla disease usually begin exhibiting hypotonia during the first year of life and go on to experience progressive neurological problems. Signs and symptoms of Salla disease include intellectual disability and developmental delay, seizures, problems with movement and balance (ataxia), abnormal tensing of the muscles (spasticity), and involuntary slow, sinuous movements of the limbs (athetosis). Individuals with Salla disease usually survive into adulthood. People with intermediate severe Salla disease have signs and symptoms that fall between those of ISSD and Salla disease in severity.
    [Show full text]
  • A Defective Response to Hedgehog Signaling in Disorders of Cholesterol Biosynthesis
    letter A defective response to Hedgehog signaling in disorders of cholesterol biosynthesis Michael K. Cooper1,2,5, Christopher A. Wassif3, Patrycja A. Krakowiak3, Jussi Taipale1, Ruoyu Gong1, Richard I. Kelley4, Forbes D. Porter3 & Philip A. Beachy1 Published online 24 March 2003; doi:10.1038/ng1134 Smith–Lemli–Opitz syndrome (SLOS), desmosterolosis and lath- additional role for cholesterol in Hh signal response was sug- osterolosis are human syndromes caused by defects in the final gested by the observation that cyclopamine and jervine, terato- stages of cholesterol biosynthesis. Many of the developmental genic plant alkaloids that block Hh signaling, also inhibit malformations in these syndromes occur in tissues and struc- cholesterol transport and synthesis2,3. But cyclopamine has since tures whose embryonic patterning depends on signaling by the been shown to specifically inhibit Hh signaling by binding to a Hedgehog (Hh) family of secreted proteins. Here we report that pathway component4, and the doses of these alkaloids required response to the Hh signal is compromised in mutant cells from to inhibit Hh signaling are lower than those required to block mouse models of SLOS and lathosterolosis and in normal cells cholesterol transport (ref. 5 and M.K.C., unpublished data). pharmacologically depleted of sterols. We show that decreas- To determine how cholesterol may affect Hh signaling in embry- ing levels of cellular sterols correlate with diminishing respon- onic development, we exposed chick embryos to cyclodextrin, a http://www.nature.com/naturegenetics siveness to the Hh signal. This diminished response occurs at cyclic oligosaccharide that forms non-covalent complexes with sterol levels sufficient for normal autoprocessing of Hh protein, sterols6 and can be used to extract and deplete cholesterol from liv- which requires cholesterol as cofactor and covalent adduct.
    [Show full text]
  • Datasheet: VPA00226
    Datasheet: VPA00226 Description: RABBIT ANTI ALDOA Specificity: ALDOA Format: Purified Product Type: PrecisionAb™ Polyclonal Isotype: Polyclonal IgG Quantity: 100 µl Product Details Applications This product has been reported to work in the following applications. This information is derived from testing within our laboratories, peer-reviewed publications or personal communications from the originators. Please refer to references indicated for further information. For general protocol recommendations, please visit www.bio-rad-antibodies.com/protocols. Yes No Not Determined Suggested Dilution Western Blotting 1/1000 PrecisionAb antibodies have been extensively validated for the western blot application. The antibody has been validated at the suggested dilution. Where this product has not been tested for use in a particular technique this does not necessarily exclude its use in such procedures. Further optimization may be required dependant on sample type. Target Species Human Species Cross Reacts with: Mouse, Rat Reactivity N.B. Antibody reactivity and working conditions may vary between species. Product Form Purified IgG - liquid Preparation Rabbit Ig fraction prepared by ammonium sulphate precipitation Buffer Solution Phosphate buffered saline Preservative 0.09% Sodium Azide (NaN3) Stabilisers Immunogen KLH conjugated synthetic peptide between 66-95 amino acids from the N-terminal region of human ALDOA External Database UniProt: Links P04075 Related reagents Entrez Gene: 226 ALDOA Related reagents Page 1 of 2 Synonyms ALDA Specificity Rabbit anti Human ALDOA antibody recognizes fructose-bisphosphate aldolase A, also known as epididymis secretory sperm binding protein Li 87p, fructose-1,6-bisphosphate triosephosphate-lyase, lung cancer antigen NY-LU-1 and muscle-type aldolase. Encoded by the ALDOA gene, fructose-bisphosphate aldolase A is a glycolytic enzyme that catalyzes the reversible conversion of fructose-1,6-bisphosphate to glyceraldehyde 3-phosphate and dihydroxyacetone phosphate.
    [Show full text]
  • Maladies Convention Mal
    maladies métaboliques monogéniques héréditaires rares 1 avenant à la convention avec les centres de référence – annexe OMIM # FULL NAME A. disorders of amino acid metabolism 1 261600 classical phenylketonuria and hyperphenylala- ninemia 2 261640 phenylketonuria due to PTPS deficiency 3 261630 phenylketonuria due to DHPR deficiency 4 264070 phenylketonuria due to PCD deficiency 5 128230 DOPA-responsive dystonia (TH, SPR, GCH1) 6 248600 leucinose, maple syrup urine disease (MSUD) 7 276700 tyrosinemia type 1 8 276600 tyrosinemia type 2 9 276710 tyrosinemia type 3 10 203500 alkaptonuria 11 236200 homocystinuria, B6 responsive and non responsive 12 236250 homocystinuria due to MTHFR deficiency 13 236270-250940 homocystinuria-megaloblastic anemia Cbl E & G type 14 250850 methionine S-adenosyltransferase deficiency 15 606664 glycine N-methyltransferase deficiency 16 180960 S-adenosylhomocystine hydrolase deficiency 17 237300 hyperammonemia due to CPS deficiency 18 311250 hyperammonemia due to OTC deficiency 19 215700 citrullinemia type I 20 605814-603471 citrullinemia type II 21 207900 argininosuccinic aciduria (ASL deficiency) 22 207800 argininemia (arginase deficiency) 23 237310 hyperammonemia due to NAGS deficiency 24 238970 hyperornithinemia, hyperammonemia, homocitrulli- nuria (HHH) 25 222700 lysinuric protein intolerance 26 258870 gyrate atrophy, B6 responsive or non responsive 27 238700 hyperlysinemia (alpha-aminoadipic semialdehyde synthase deficiency) 28 238300-330-310 non ketotic hyperglycinaemia 29 234500 hartnup disorder 30 601815-172480
    [Show full text]