DOCSLIB.ORG

Amino Acids & Proteins

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Amino Acids & Proteins Amino Acids & Proteins Amino Acids Amino acids are organic compounds containing both amino group & carboxyl group, those occurring in human proteins are L α-amino acids having the formula RCH(NH2)COOH & with the exception of glycine all amino acids are asymmetric . D-Amino acids that occur naturally are free D-serine& D- aspartate which present in the in brain tissue. Classification of Amino acids Over 300 amino acids occur naturally, however; only 20 of them share in the formation of proteins. Classification of amino acids either according to their R-group or to their nutritional importance. 1-Classification according to R-group(side chain). 1 2 2-Classification according to their nutritional importance All 20 amino acids present in proteins are biologically essential but not all of them are nutritionally essential, therefore, they are classified into: 3 A-Nutritionally essential amino acids :they should be supplement in diet because human body can not synthesize it , there deficiencies lead to kwashiorkor (protein malnutrition) & marasmus (protein & energy malnutrition). B-Nutritionally nonessential amino acids : human body can synthesize it , therefore , it’s not essential to be supplied in the diet. R-group It determines the property of amino acid in peptide formation as: 1-Since glycine is smallest amino acid, therefore, it can accommodate in places inaccessible to other amino acids in the formation of peptide. 4 2-Hydrophobic R-group of alanine, valine, leucine, Isoleucine, & aromatic R-groups of phenylalanine , tyrosine & tryptophan make them in the interior of protein. 3-The charged R-group of basic & acidic amino acids stabilize protein conformation through ionic interaction or salt-bridge. In Vivo Synthesis of Nutritionally Nonessential Amino Acids Glutamate & Glutamine: Reductive amination of α- ketoglutarate is catalyzed by glutamate dehydrogenase enzyme forming glutamate, this reaction is reversible. Amidation of glutamate to glutamine is catalyzed by glutamine synthetase enzyme, this irreversible reaction requires ATP. Alanine: By amination of pyruvate forming alanine, the amino donor may be glutamate or aspartate, this reversible transamination reaction is catalyzed by transaminase enzyme. Aspartate & Asparagine: By amination of oxaloacetate forming aspartate, the amino donor may be alanine; this 5 reversible transamination reaction is catalyzed by transaminase enzyme. Amidation of aspartate to asparagine is catalyzed by asparagine synthetase enzyme, this irreversible reaction requires ATP and it’s resemble amidation of glutamate , however , glutamine rather than ammonium ion, provides the nitrogen for this amidation. Serine:Formed from glycolytic intermediate 3-phosphoglycerate Glycine : Formed from glyoxylate , glutamate or alanine by a reversible reaction catalyzed by glycine aminotransferases ,it can produce also from choline & serine. Proline: Formed from glutamate. Cysteine: Formed from methionine as discussed later. Tyrosine: phenylalanine converted to tyrosine by irreversible reaction catalyzed by phenylalanine hydroxylase enzyme; since this reaction is irreversible ,therefore, dietary tyrosine can not replace phenylalanine. 6 Hydroxyproline & Hydroxylysine : They are important in posttranslational processing of collagen & not necessary for protein synthesis .Formed by hydroxylation of proline & lysine in a reaction catalyzed by prolyl hydroxylase &lysyl- hydroxylase enzymes respectively, it require vitamin C as cofactor , therefore , deficiency of vitamin C lead to scurvy. Proteins Formation of peptides Link of amino acids lead to the formation of peptides. -If the chain formed from up to five amino acids the structure is called oligopeptide or called dipeptide, tripeptide, tetrapeptide & so on if consist from 2,3,4 amino acids respectively. -If the chain formed from 6-30 amino acids the structure is called polypeptide. -If the chain formed from larger than 30 amino acids the structure is called protein. Classifications of Proteins ►I-Initial classification according to their properties as: 1-Solubility : 2-Shape : 7 A-Globular proteins: roughly spherical or ovoid in shape with their axial ratios (ratio of their longest to shortest dimensions) of not more than 3 with tendency to be soluble in physiological fluids(because it is compact with hydrophilic R-group face outward ), it represent nearly all proteins of interest in clinical chemistry like hemoglobin , enzymes & plasma protein except fibrinogen. B-Fibrous proteins: their axial ratios 10 or more with tendency to be insoluble in physiological fluids e.g fibrinogen. 3-Presence of nonproteins groups (prosthetic groups): these prosthetic groups are bound to protein forming conjugated proteins , the conjugated proteins without prosthetic groups are called apoproteins. prosthetic group + apoprotein = conjugated protein example: A-lipid + protein = lipoproteins B- CHO+protein=glycoprotein(if CHO 5-15%)& mucoprotein (if CHO 15-75%) C-metal ion+ protein = metalloprotein as hemoglobin . ►II-Nowadays with the development of determination of amino acids sequences of proteins more precise classification depend on homology of sequence & structure of amino acids in protein , however , early classification still in use. Orders of Protein Structure Conformation of proteins into the following orders of structure is necessary to maintain their function & physical property. 1-Primary structure 2-Secondary structure 3-Tertiary structure 4-Quaternary structure Primary structure Represent the sequence of amino acids in polypeptide chain , its genetically determined, formed by peptide-bonds that linked amino acids together by connecting amino group of one amino 8 acid with a carboxyl group of another leaving only one free amino group & carboxyl group at both extreme of protein, the amino acids present in peptide are called aminoacyl residues & are named by replacing the ate or ine suffixes of free amino acids with yl e.g..(alanyl,aspartyl,glutamine) the ine ending of glutamine indicates that it is carboxyl group is not involved in the peptide bond formation (extreme of protein). Secondary structure Generally peptide bonds of protein restrict this secondary conformation , however , free rotation is possible only in a bond that link : a) α-carbon to the carbonyl carbon b) α-carbon to the nitrogen This secondary structure has the following conformations: 1-Alpha Helix 2- Beta Sheet 3-Loops & Bends 1-Alpha Helix: look like cylinder with R-group of each aminoacyl residue face outward. 9 2-The Beta Sheet: look like zigzag or pleated pattern with R- groups of adjacent residues point in opposite directions , unlike the compact backbone of α-helix the backbone of Beta Sheet is highly extended , most Beta Sheet are twisted & not perfectly flat forming the core of globular proteins. 3-Loops & Bends : It refer to the short segments of amino acids that joint two units of secondary structure & it represent the key of biological role of that protein. Tertiary structure Secondary structural features as alpha-helix , beta-sheet , loops & bends are assemble to form domain which represent a section of protein structure sufficient to perform a particular physical or chemical task. Some polypeptides are small consist from a single domain as myoglobin while other are large consist from many domains. The tertiary structure represents how secondary structural features are assemble to form domain & how these domains relate spatially to one another. 11 Quaternary structure Some proteins are assembled from more than one polypeptide or protomer. Quaternary structure defines the polypeptide composition of protomer & for those protein containing more than one protomer the spatial relationships between these protomers . Protein with a single protomer called monomeric protein. Protein with two protomers called dimeric protein , these two protomers either identical ((homodimeric)) or not identical ((heterodimeric)). Greek letters ((α,β,γ… )) are used to distinguish different protomers in a single protein. Pathology of Altered Protein Conformation 1-Creutzfelt-jakob disease : Its fatal neurodegenerative disease resulting from alteration of protein conformation in neural cells , the pathogenesis of disease is still not clear probably due to chromosomal changes ((chromosome 20)) . 2-Alzheimer's disease: It characterize by senile plaques in the brain with alteration in neuron protein conformation, the pathogenesis of disease is still not clear. 3-Thalassemia: caused by genetic defects that impair the synthesis of one of the polypeptide subunits (α or β) of hemoglobin. Biological Functions of Proteins 1-Enzymes: catalyze biochemical reactions. 2-Peptide hormones : regulate metabolism. 3-Antibodies & Complements : defense mechanism . 4-Albumin : maintain oncotic pressure of plasma. 5-Many plasma proteins like albumin transport vitamins, metals, hormones & drugs in the blood often serving as reservoirs . 6-Hemoglobin : carry oxygen. 7-Coagulation factors : affect haemostasis. 8-Structural proteins as keratin & collagen. 9-Contractile proteins as myosin. 10-Storage proteins as ferritin that store iron. 11 Digestion & Absorption of Proteins Few bonds are accessible to the proteolytic digestive enzymes (proteases) that catalyze hydrolysis of peptide bonds, without prior denaturation of dietary proteins (by heat in cooking & by the action of gastric acid). There are two main classes of proteases enzymes which are:- A-Endopeptidases:- hydrolyze peptide bonds between specific amino acids throughout the molecule.
Load more

Recommended publications
  • 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]
  • Genes Investigated
    BabyNEXTTM EXTENDED Investigated genes and associated diseases Gene Disease OMIM OMIM Condition RUSP gene Disease ABCC8 Familial hyperinsulinism 600509 256450 Metabolic disorder - ABCC8-related Inborn error of amino acid metabolism ABCD1 Adrenoleukodystrophy 300371 300100 Miscellaneous RUSP multisystem (C) * diseases ABCD4 Methylmalonic aciduria and 603214 614857 Metabolic disorder - homocystinuria, cblJ type Inborn error of amino acid metabolism ACAD8 Isobutyryl-CoA 604773 611283 Metabolic Disorder - RUSP dehydrogenase deficiency Inborn error of (S) ** organic acid metabolism ACAD9 acyl-CoA dehydrogenase-9 611103 611126 Metabolic Disorder - (ACAD9) deficiency Inborn error of fatty acid metabolism ACADM Acyl-CoA dehydrogenase, 607008 201450 Metabolic Disorder - RUSP medium chain, deficiency of Inborn error of fatty (C) acid metabolism ACADS Acyl-CoA dehydrogenase, 606885 201470 Metabolic Disorder - RUSP short-chain, deficiency of Inborn error of fatty (S) acid metabolism ACADSB 2-methylbutyrylglycinuria 600301 610006 Metabolic Disorder - RUSP Inborn error of (S) organic acid metabolism ACADVL very long-chain acyl-CoA 609575 201475 Metabolic Disorder - RUSP dehydrogenase deficiency Inborn error of fatty (C) acid metabolism ACAT1 Alpha-methylacetoacetic 607809 203750 Metabolic Disorder - RUSP aciduria Inborn error of (C) organic acid metabolism ACSF3 Combined malonic and 614245 614265 Metabolic Disorder - methylmalonic aciduria Inborn error of organic acid metabolism 1 ADA Severe combined 608958 102700 Primary RUSP immunodeficiency due
    [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: georgianne.arnold4@chp.edu. 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]
  • Annual Symposium of the Society for the Study of Inborn Errors of Metabolism Birmingham, UK, 4 – 7 September 2012
    J Inherit Metab Dis (2012) 35 (Suppl 1):S1–S182 DOI 10.1007/s10545-012-9512-z ABSTRACTS Annual Symposium of the Society for the Study of Inborn Errors of Metabolism Birmingham, UK, 4 – 7 September 2012 This supplement was not sponsored by outside commercial interests. It was funded entirely by the SSIEM. 01. Amino Acids and PKU O-002 NATURAL INHIBITORS OF CARNOSINASE (CN1) O-001 Peters V1 ,AdelmannK2 ,YardB2 , Klingbeil K1 ,SchmittCP1 , Zschocke J3 3-HYDROXYISOBUTYRIC ACID DEHYDROGENASE DEFICIENCY: 1Zentrum für Kinder- und Jugendmedizin de, Heidelberg, Germany IDENTIFICATION OF A NEW INBORN ERROR OF VALINE 2Universitätsklinik, Mannheim, Germany METABOLISM 3Humangenetik, Innsbruck, Austria Wanders RJA1 , Ruiter JPN1 , Loupatty F.1 , Ferdinandusse S.1 , Waterham HR1 , Pasquini E.1 Background: Carnosinase degrades histidine-containing dipeptides 1Div Metab Dis, Univ Child Hosp, Amsterdam, Netherlands such as carnosine and anserine which are known to have several protective functions, especially as antioxidant agents. We recently Background, Objectives: Until now only few patients with an established showed that low carnosinase activities protect from diabetic nephrop- defect in the valine degradation pathway have been identified. Known athy, probably due to higher histidine-dipeptide concentrations. We deficiencies include 3-hydroxyisobutyryl-CoA hydrolase deficiency and now characterized the carnosinase metabolism in children and identi- methylmalonic semialdehyde dehydrogenase (MMSADH) deficiency. On fied natural inhibitors of carnosinase. the other hand many patients with 3-hydroxyisobutyric aciduria have been Results: Whereas serum carnosinase activity and protein concentrations described with a presumed defect in the valine degradation pathway. To correlate in adults, children have lower carnosinase activity although pro- identify the enzymatic and molecular defect in a group of patients with 3- tein concentrations were within the same level as for adults.
    [Show full text]
  • Omics Knowledgebase for Mammalian Cellular Signaling Pathways
    bioRxiv preprint doi: https://doi.org/10.1101/401729; this version posted August 27, 2018. 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. The Signaling Pathways Project: an integrated ‘omics knowledgebase for mammalian cellular signaling pathways Scott Ochsner, David Abraham*, Kirt Martin*, Wei Ding, Apollo McOwiti, Zichen Wang, Kaitlyn Andreano, Ross A. Hamilton, Yue Chen, Angelica Hamilton, Marin L. Gantner, Michael Dehart, Shijing Qu, Susan G. Hilsenbeck, Lauren B. Becnel, Dave Bridges, Avi Ma’ayan, Janice M. Huss, Fabio Stossi, Charles E. Foulds, Anastasia Kralli, Donald P. McDonnell and Neil J. McKenna Address Correspondence To: Neil J. McKenna Department of Molecular and Cellular Biology Baylor College of Medicine Houston, TX 77030 USA e: nmckenna@bcm.edu t: 713-798-8568 *These authors contributed equally to this study 1 bioRxiv preprint doi: https://doi.org/10.1101/401729; this version posted August 27, 2018. 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. Summary Public transcriptomic and ChIP-Seq datasets have the potential to illuminate facets of transcriptional regulation by mammalian cellular signaling pathways not yet explored in the research literature. Unfortunately, a variety of obstacles prevent routine re-use of these datasets by bench biologists for hypothesis generation and data validation. Here, we designed a web knowledgebase, the Signaling Pathways Project (SPP), which incorporates stable community classifications of three major categories of cellular signaling pathway node (receptors, enzymes and transcription factors) and the bioactive small molecules (BSMs) known to modulate their functions.
    [Show full text]
  • Amino Acid Disorders Detected by Quantitative Amino Acid HPLC Analysis in Thailand: an Eight-Year Experience
    ارا ه ت ه از $&% #ت "! Clinica Chimica Acta 413 (2012) 1141–1144 Contents lists available at SciVerse ScienceDirect Clinica Chimica Acta journal homepage: www.elsevier.com/locate/clinchim Amino acid disorders detected by quantitative amino acid HPLC analysis in Thailand: An eight-year experience Nithiwat Vatanavicharn ⁎, Pisanu Ratanarak, Somporn Liammongkolkul, Achara Sathienkijkanchai, Pornswan Wasant Division of Medical Genetics, Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand article info abstract Article history: Background: Amino acid disorders are a major group of inborn errors of metabolism (IEM) with variable clin- Received 13 October 2011 ical presentations. This study was aimed to provide the data of amino acid disorders detected in high-risk Received in revised form 16 March 2012 Thai patients referred to our metabolic lab from all over the country. Accepted 20 March 2012 Methods: From 2001 to 2009, we analyzed amino acids by HPLC in 1214 plasma and cerebrospinal fluid spec- Available online 23 March 2012 imens. These specimens were obtained from patients with clinical suspicion of IEM or with positive newborn screening. The clinical data of the patients with confirmed diagnoses of amino acid disorders were also ana- Keywords: lyzed. Amino acid disorders HPLC Results: Fifty-eight patients were diagnosed with amino acid disorders, including 20 cases (34.5%) with maple Thailand syrup urine disease, 13 (22.4%) with phenylketonuria and hyperphenylalaninemia, 13 (22.4%) with nonke- totic hyperglycinemia, 9 (15.5%) with urea cycle defects, 2 (3.4%) with classical homocystinuria, and 1 (1.7%) with ornithine aminotransferase deficiency. There was considerable delay in diagnoses which led to poor outcomes in most patients.
    [Show full text]
  • Enteral Nutrition
    UnitedHealthcare® Commercial Coverage Determination Guideline Enteral Nutrition Guideline Number: CDG.027.03 Effective Date: July 1, 2021 Instructions for Use Table of Contents Page Related Commercial Policies Coverage Rationale ........................................................................... 1 • Durable Medical Equipment, Orthotics, Medical Definitions ........................................................................................... 2 Supplies and Repairs/ Replacements Applicable Codes .............................................................................. 3 References .......................................................................................10 Community Plan Policy Guideline History/Revision Information .......................................10 • Oral and Enteral Nutrition Instructions for Use .........................................................................10 Coverage Rationale Indications for Coverage Certain plans may include coverage for enteral nutrition (enteral formulas and low protein modified food products). Refer to the member specific benefit plan document to determine if this coverage applies. For Plans with Language that Cover Enteral Nutrition For plans that cover enteral nutrition, if there is a difference between a member specific benefit plan document and the information below, the member specific benefit plan document should be used for making benefit determinations. Note: Check state mandate applicability before proceeding with the following. Benefits are provided
    [Show full text]
  • Catabolism of the Carbon Skeletons of Amino Acids
    Bio. 2. ASPU. Lectu.3. Prof. Dr. F. ALQuobaili Catabolism of the Carbon Skeletons of Amino Acids • Biomedical Importance ‐ The metabolic diseases or "inborn errors of metabolism" associated with conversion of the carbon skeletons of the common L ‐‐amino acids to amphibolic intermediates can result in irreversible brain damage and .(ﺍﻟﻭﻓﺎﺓ) early mortality ‐ Prenatal or early postnatal detection and timely initiation of treatment thus are essential. Almost all states conduct screening tests for up to as many as 30 metabolic diseases. ‐ The best screening tests use tandem mass spectrometry to detect, in a few drops of neonate blood, catabolites suggestive of a metabolic defect. ‐ Treatment consists primarily of feeding diets low in the amino acids whose catabolism is impaired. • Transamination Typically Initiates Amino Acid Catabolism Removal of ‐amino nitrogen by transamination is the first catabolic reaction of amino acids except for proline, hydroxyproline, threonine, and lysine. The hydrocarbon skeleton that remains is then degraded to amphibolic intermediates. • Asparagine, Aspartate, Glutamine, and Glutamate All four carbons of asparagine and aspartate form oxaloacetate. Analogous reactions convert glutamine and glutamate to ‐ ketoglutarate. No metabolic defects are associated with the catabolism of these four amino acids. • Proline The catabolism of proline takes place in mitochodria. Since proline does not participate in transamination, the nitrogen of this imino acid is retained throughout its oxidation to 1‐ pyrolline‐5‐carboxylate, ring opening to glutamate‐‐ semialdehyde, and oxidation to glutamate, and is only removed during transamination of glutamate to ‐ketoglutarate. There are two metabolic disorders of proline catabolism. Both types are inherited as autosomal recessive traits, and are consistent with a normal adult life.
    [Show full text]
  • Attachment a Rare and Expensive Disease List As of December 27, 2010 ICD-9 Age Disease Guidelines Code Group 042
    Attachment A Rare and Expensive Disease List as of December 27, 2010 ICD-9 Age Disease Guidelines Code Group 042. Symptomatic HIV disease/AIDS 0-20 (A) A child <18 mos. who is known to be HIV (pediatric) seropositive or born to an HIV-infected mother and: * Has positive results on two separate specimens (excluding cord blood) from any of the following HIV detection tests: --HIV culture (2 separate cultures) --HIV polymerase chain reaction (PCR) --HIV antigen (p24) N.B. Repeated testing in first 6 mos. of life; optimal timing is age 1 month and age 4-6 mos. or * Meets criteria for Acquired Immunodeficiency Syndrome (AIDS) diagnosis based on the 1987 AIDS surveillance case definition V08 Asymptomatic HIV status 0-20 (B) A child >18 mos. born to an HIV-infected (pediatric) mother or any child infected by blood, blood products, or other known modes of transmission (e.g., sexual contact) who: * Is HIV-antibody positive by confirmatory Western blot or immunofluorescense assay (IFA) or * Meets any of the criteria in (A) above 795.71 Infant with inconclusive HIV result 0-12 (E) A child who does not meet the criteria above months who: * Is HIV seropositive by ELISA and confirmatory Western blot or IFA and is 18 mos. or less in age at the time of the test or * Has unknown antibody status, but was born to a mother known to be infected with HIV 270.0 Disturbances of amino-acid 0-20 Clinical history and physical exam; laboratory transport studies supporting diagnosis. Subspecialist Cystinosis consultation note may be required.
    [Show full text]
  • Diseases Catalogue
    Diseases catalogue AA Disorders of amino acid metabolism OMIM Group of disorders affecting genes that codify proteins involved in the catabolism of amino acids or in the functional maintenance of the different coenzymes. AA Alkaptonuria: homogentisate dioxygenase deficiency 203500 AA Phenylketonuria: phenylalanine hydroxylase (PAH) 261600 AA Defects of tetrahydrobiopterine (BH 4) metabolism: AA 6-Piruvoyl-tetrahydropterin synthase deficiency (PTS) 261640 AA Dihydropteridine reductase deficiency (DHPR) 261630 AA Pterin-carbinolamine dehydratase 126090 AA GTP cyclohydrolase I deficiency (GCH1) (autosomal recessive) 233910 AA GTP cyclohydrolase I deficiency (GCH1) (autosomal dominant): Segawa syndrome 600225 AA Sepiapterin reductase deficiency (SPR) 182125 AA Defects of sulfur amino acid metabolism: AA N(5,10)-methylene-tetrahydrofolate reductase deficiency (MTHFR) 236250 AA Homocystinuria due to cystathionine beta-synthase deficiency (CBS) 236200 AA Methionine adenosyltransferase deficiency 250850 AA Methionine synthase deficiency (MTR, cblG) 250940 AA Methionine synthase reductase deficiency; (MTRR, CblE) 236270 AA Sulfite oxidase deficiency 272300 AA Molybdenum cofactor deficiency: combined deficiency of sulfite oxidase and xanthine oxidase 252150 AA S-adenosylhomocysteine hydrolase deficiency 180960 AA Cystathioninuria 219500 AA Hyperhomocysteinemia 603174 AA Defects of gamma-glutathione cycle: glutathione synthetase deficiency (5-oxo-prolinuria) 266130 AA Defects of histidine metabolism: Histidinemia 235800 AA Defects of lysine and
    [Show full text]
  • BOOK REVIEWS 567 Prenatal Diagnosis and Selective Abortion
    BOOK REVIEWS 567 Prenatal Diagnosis and Selective Abortion. By H. HARRIS. London: Nuffield Provincial Hospitals Trust, 1974. Pp. 101. 11.75. U.S. publisher, Harvard University Press. The recent introduction of prenatal detection of genetic disorders has raised a variety of ethical and biological questions. This book not only reviews a number of problems with intrauterine diagnosis, including the scope of the procedure and its effects on the incidence of genetic diseases, but it also raises a number of ethical questions which have generated considerable discussion in both professional and nonprofessional fields. The text is authored by an acknowledged expert in the field of human genetics. Harris has divided his thesis into three major chapters. The first presents an overview of the present state of knowledge of intrauterine diagnosis as it relates to chromosomal abnor- malities, X-linked disorders, metabolic diseases, and congenital malformations. This section does not contain an extensive review of the literature but does highlight many of the more important aspects. The second section deals with effects on the incidence of genetic disease. It outlines both the potential short- and long-term effects that are expected to follow from selective abortion whether the abnormality is a single gene or classical Mendelian condition, a gross chromosomal defect, or a disorder regarded as multifactorial in origin. The last section, which is the most interesting in my opinion, deals with the question of ethics. Harris not only clearly points out the ethical and moral questions of selective abortion, including the undesirable aspects, but he also describes the visible benefits which, in his opinion, make intrauterine detection a valuable advance in medicine.
    [Show full text]
  • Hematologic Aberrations in Metabolic Diseases
    ANNALS OF CLINICAL AND LABORATORY SCIENCE, Vol. 10, No. 6 Copyright © 1980, Institute for Clinical Science, Inc. Hematologic Aberrations in Metabolic Diseases BRUCE A. BUEHLER, M.D. Department of Pediatric Metabolism University of Utah College of Medicine Salt Lake City, UT 84132 ABSTRACT This study of enzyme deficiencies and hematologic aberrations in meta­ bolic diseases includes disorders of amino acidopathies, lipid disease, al­ binism, carbohydrates, and mucopolysaccharidosis. Introduction clinical evidence of marked hematologi­ cal aberrations. This list is divided into The definition of metabolic disease has problems of amino acid metabolism, lipid changed markedly during this century. disease, albinism, carbohydrate disorders When Sir Archibald Garrod gave the orig­ and, finally, the mucopolysaccharidoses. inal Croonian lectures in 1902, metabolic disease was synonomous with the term Amino Acidopathies “inborn errors of metabolism,” but pres­ ent concepts have expanded to include all A c id e m i a s diseases that affect availability of biologi­ In 1971, Hsia6 described the enzyme cal substrates or energy production. It deficiency that accounted for ketotic would be impossible to summarize all the hyperglycinemia. Fibroblasts from pa­ metabolic diseases that may have a pri­ tients with this disease were found to be mary or secondary effect on hemato- deficient in propionyl CoA carboxylase poiesis; therefore, this study has been ar­ activity, and the toxic product responsible bitrarily limited to diseases which have a for the clinical symptoms was propionic known or postulated genetic enzyme de­ acid. Since this discovery, the disease is ficiency as the primary aberration. now referred to as propionic acidemia. Pathological states such as chronic liver The dietary precursors of propionyl disease, ingestion of toxins, or dietary de­ CoA and propionic acid are valine, ficiency states have not been considered leucine, isoleucine, methionine, within the scope of this text.
    [Show full text]