Antenatal Diagnosis of Inborn Errors Ofmetabolism

Total Page:16

File Type:pdf, Size:1020Kb

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. specialised fetal diagnostic units. Fortunately for many inborn errors the metabo- lic defect is generalised and both amniotic and chorion villus cells can be used as a diagnostic FETAL BLOOD SAMPLING tissue. Fetal blood sampling could be used for the ante- Before contemplating prenatal diagnosis it is natal diagnosis of many inborn errors. The essential that a firm biochemical diagnosis has sample, however, tends to be collected late in http://adc.bmj.com/ been established in the index case. It is unsafe to pregnancy and the technique is probably best rely only on a clinical or histological diagnosis as reserved as a back up in case of failed amniotic many of the inherited disorders share a similar fluid cell culture. phenotype. To ease interpretation of results obtained on the fetus it is necessary to know the heterozygote levels of enzyme activity in the AMNIOCENTESIS parents; occasionally these are remarkably low Amniocentesis has been the most common pro- on September 30, 2021 by guest. Protected copyright. and can lead to difficulties in ascribing fetal cedure for antenatal diagnosis of metabolic dis- genotype. ease. Both the cell free amniotic fluid and cul- The properties of some enzymes are appreci- tured and uncultured amniotic fluid cells are ably different when studied at different times of useful in diagnosis. gestation. In addition, the activity obtained The procedure is usually performed at 15-16 from chorion villus material may be very diffe- weeks' gestation and most analyses can be per- rent from that obtained on amniotic fluid cells. formed within two to three weeks of culture. It is essential that the correct tissue is collected First trimester amniocentesis has been attemp- at the most appropriate time. Liaison with the ted to allow earlier diagnosis, but the smaller laboratory staff performing the test is manda- sample size and possible variation in enzyme tory if mistakes are to be avoided. activity at the earlier stage of pregnancy have Prenatal testing by analysis of fetal DNA introduced variables that need to be studied by either a gene specific DNA probe or gene before the technique can be widely applied. tracking using restriction fragment length poly- (1) Cell free amniotic fluid can be used to morphisms (RFLPs) requires proband DNA detect a number of intermediary metabolites in Willink Biochemical for comparison. This underlies the importance many inborn errors. Where possible this techni- Genetics Unit, Royal Manchester of establishing fibroblast cultures from all que should be backed by specific enzyme analy- Children's Hospital, patients diagnosed as having a metabolic dis- sis, but for many conditions does allow a quick Pendlebury order as well as ensuring that blood is taken diagnosis. It is particularily relevant for organic Manchester M27 IHA from M A Cleary all relevant family members for DNA acid disorders using stable isotope dilution gas J E Wraith extraction and storage. chromatography with mass spectrometry and Correspondence to: Most prenatal testing for metabolic disease is selected ion monitoring. -Dr Wraith. performed in a few specialised laboratories. In mucopolysaccharide disorders the pattern Antenataldiagnosisofinborn errorsofmetabolism 817 of excess glycosaminoglycan excretion can be with the technique include the possibility of Arch Dis Child: first published as 10.1136/adc.66.7_Spec_No.816 on 1 July 1991. Downloaded from detected by two dimensional electrophoresis maternal contamination and differences in and this can form the basis of a reliable antena- enzyme activity in this tissue as compared with tal test for this group of conditions. skin fibroblasts or cultured amniotic fluid cells. (2) Amniotic fluid cells in culture are a com- Despite these possible limitations most prenatal mon material used in antenatal diagnosis. In diagnoses for inborn errors are performed on most cases the enzyme activity obtained in this chorion villus samples. tissue mirrors that obtained in cultured skin fibroblasts. As well as direct enzyme assay, radiolabelled incorporation studies can be Specific inborn errors of metabolism performed on the cultured cells and a wide The appendix lists the specific inborn error, the range of disorders detected. Contamination by biochemical defect, chromosome location of the mycoplasma or other organisms is the biggest gene mutation where known, and the test used threat to antenatal diagnosis by this method. for antenatal diagnosis. Where antenatal diagnosis has been successfully achieved the method used is clearly shown. For some dis- CHORION VILLUS BIOPSY orders prenatal diagnosis is theoretically poss- Chorion villus biopsy offers the advantage of ible, although to the authors' knowledge not as first trimester diagnosis. Direct analysis of yet successfully performed. In this case the enzyme activity on fresh uncultured villus tissue most likely tissue and method are indicated with usually allows a result to be available within 24- the rider, 'possible'. The key to the abbrevia- 48 hours of the procedure. Problems associated tions used is shown at the end of the appendix. Appendix Specific inborn errors ofmetabolism Condition Enzyme deficiency Chromosome Prenatal location diagnosis (A) CARBOHYDRATE METABOLISM (i) Galactose Galactokinase deficiency Galactokinase 17q21-q22 AF, CVB 'Classical' galactosaemia Galactose-1-phosphate- 9p13 AF, CVB uridyltransferase Epimerase deficiency UDP-Galactose-4-epimerase lpter-p32 Poss CC (ii) Fructose Hereditary fructose intolerance Aldolase B 9q22 Poss DNA Fructose 1-6 bisphosphatase Frutose 1-6 bisphosphatase No http://adc.bmj.com/ deficiency (iii) Glycogen storage disease Ia Von Gierke Glucose-6-phosphatase Poss FT b Glucose-6-phosphatase Poss FT translocase (TI) c Glucose-6-phosphatase Poss FT on September 30, 2021 by guest. Protected copyright. translocase (T2) II Pompe Lysosomal acid glucosidase 17q23 AF, CVB III Debrancher enzyme Amylo-1-6-glucosidase AF, CVB deficiency IV Brancher enzyme deficiency 1-4-Glucan 6-glycosyl- AF, CVB transferase V McCardle Muscle phosphorylase 1 lql3-qter No VI Liver phosphorylase Liver phosphorylase 14 Poss FT deficiency VII Phosphofructokinase Phosphofructokinase lcen-q32 No deficiency IXa Phosphorylase kinase Phosphorylase kinase 16ql2-ql3-1 Poss FT (recessive) IXb Phosphorylase kinase Phosphorylase kinase Xql2-ql3 Poss FT (X linked) (B) AMINO ACID METABOLISM (i) Phenylalanine 'Classical' phenylketonuria Phenylalanine hydroxylase 12q22-q24- 1 DNA Tetrabiopterin homoeostasis Dihydropteridine reductase 4pl53 AF, CVB Tetrabiopterin synthesis Guanosine triphosphate MET cyclohydrolase 6-Pyruvoyltetrahydropterin MET synthase 818 Cleary, Wraith Condition Enzyme deficiency Chromosome Prenatal Arch Dis Child: first published as 10.1136/adc.66.7_Spec_No.816 on 1 July 1991. Downloaded from location diagnosis (ii) Methionine Homocystinuria Cystathionine synthase 21q22-q22-1 AF, CVB (iii) Tyrosine Tyrosinaemia I Fumarylacetoacetate hydrolase 15q23-q25 AF, CVB Tyrosinaemia II Tyrosine aminotransferase 16q22-q22 1 No (iv) Valine, leucine, isoleucine Maple syrup urine disease Branched chain ketoacid 19ql3-1-ql3-2 AF, CVB dehydrogenase (v) Glycine Non-ketotic hyperglycinaemia Glycine cleavage system 9p22 CVB (vi) Lysine Hyperlysinaemia Aminoadipic semialdehyde UNK synthase (vii) Proline Hyperprolinaemia I Proline oxidase UNK Hyperprolinaemia II Pyrroline-5-carboxylate UNK dehydrogenase Hyperimidodipeptiduria Prolidase 19ql2-ql3-2 Poss CC (viii) Ornithine Gyrate atrophy of the choroid Ornithine aminotransferase 10q26 Poss CC and retina Hyperornithinaemia- Basic defect unknown No hyperammonaemia- homocitrullinaemia (HHH syndrome) (C) UREA CYCLE DISORDERS N-acetylglutamate synthetase N-acetylglutamate synthetase
Recommended publications
  • Clinical Applications and Implications of Common and Founder Mutations in Indian Subpopulations
    REVIEW OFFICIAL JOURNAL Clinical Applications and Implications of Common and Founder Mutations in Indian Subpopulations www.hgvs.org Arunkanth Ankala,1∗ † Parag M. Tamhankar,2 † C. Alexander Valencia,3,4 Krishna K. Rayam,5 Manisha M. Kumar,5 and Madhuri R. Hegde1 1Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia; 2ICMR Genetic Research Center, National Institute for Research in Reproductive Health, Mumbai, Maharashtra, India; 3Division of Human Genetics, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio; 4Department of Pediatrics, University of Cincinnati Medical School, Cincinnati, Ohio; 5Department of Biosciences, CMR Institute of Management Studies, Bangalore, Karnataka, India Communicated by Arupa Ganguly Received 24 October 2013; accepted revised manuscript 16 September 2014. Published online 27 November 2014 in Wiley Online Library (www.wiley.com/humanmutation). DOI: 10.1002/humu.22704 that include a lack of widespread awareness about genetic disorders in the general population and the scarcity of specialized medical ABSTRACT: South Asian Indians represent a sixth of the world’s population and are a racially, geographically, and professionals and affordable genetic tests. Seeking a molecular di- genetically diverse people. Their unique anthropological agnosis and understanding the risk estimates are critical to making structure, prevailing caste system, and ancient religious sound reproductive choices, especially in families with an affected practices have all impacted the genetic composition of most individual. Adding to this adversity is the absence of a properly func- of the current-day Indian population. With the evolving tioning social health care system and insufficient encouragement socio-religious and economic activities of the subsects and of individual health insurance by the government.
    [Show full text]
  • Oxalate Loading Test: a Screening Test for Steatorrhoea
    Gut: first published as 10.1136/gut.20.12.1089 on 1 December 1979. Downloaded from Gut, 1979, 20, 1089-1094 Oxalate loading test: a screening test for steatorrhoea D. S. RAMPTON', G. P. KASIDAS, G. ALAN ROSE, AND MARTIN SARNER2 From University College Hospital, London, St. Peter's Hospitals and Institute of Urology, London SUMMARY To investigate the possibility of measuring urinary oxalate output instead of faecal fat excretion as an outpatient screening test for steatorrhoea, we determined 24 hour urinary oxalate and five day faecal fat excretion before and during an oral load of sodium oxalate 600 mg daily (oxalate 4-44 mmol), in 32 patients with suspected malabsorption on a diet containing oxalate 30 mg (0-33 mmol), fat 50 g (180 mmol), and calcium 1 g (25 mmol). Nineteen patients proved to have steatorrhoea (mean faecal fat 62 mmol/24 h, range 19-186 mmol) of varying aetiologies. On the diet alone, urinary oxalate was raised in only nine of these patients (mean 0 25 mmol/24 h, range 0-08-059 mmol) (normal <0 20). By contrast, when the diet was supplemented with oral sodium oxalate, all 19 patients with steatorrhoea had hyperoxaluria (mean 0-91 mmol/24 h, range 046- 1P44 mmol) (normal <0-44). There was a significant positive linear relationship between urinary oxalate and faecal fat when the 32 patients were on the high oxalate intake (r=0*73, P <0.001), but not when they were on the low oxalate intake. Mean percentage absorption of orally administered oxalate was 58+09% (±1 SD) in normal subjects and 14-7+6-0% (P <0.002) in patients with steatorrhoea.
    [Show full text]
  • Hereditary Galactokinase Deficiency J
    Arch Dis Child: first published as 10.1136/adc.46.248.465 on 1 August 1971. Downloaded from Alrchives of Disease in Childhood, 1971, 46, 465. Hereditary Galactokinase Deficiency J. G. H. COOK, N. A. DON, and TREVOR P. MANN From the Royal Alexandra Hospital for Sick Children, Brighton, Sussex Cook, J. G. H., Don, N. A., and Mann, T. P. (1971). Archives of Disease in Childhood, 46, 465. Hereditary galactokinase deficiency. A baby with galactokinase deficiency, a recessive inborn error of galactose metabolism, is des- cribed. The case is exceptional in that there was no evidence of gypsy blood in the family concerned. The investigation of neonatal hyperbilirubinaemia led to the discovery of galactosuria. As noted by others, the paucity of presenting features makes early diagnosis difficult, and detection by biochemical screening seems desirable. Cataract formation, of early onset, appears to be the only severe persisting complication and may be due to the biosynthesis and accumulation of galactitol in the lens. Ophthalmic surgeons need to be aware of this enzyme defect, because with early diagnosis and dietary treatment these lens changes should be reversible. Galactokinase catalyses the conversion of galac- and galactose diabetes had been made in this tose to galactose-l-phosphate, the first of three patient (Fanconi, 1933). In adulthood he was steps in the pathway by which galactose is converted found to have glycosuria as well as galactosuria, and copyright. to glucose (Fig.). an unexpectedly high level of urinary galactitol was detected. He was of average intelligence, and his handicaps, apart from poor vision, appeared to be (1) Galactose Gackinase Galactose-I-phosphate due to neurofibromatosis.
    [Show full text]
  • 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]
  • Blueprint Genetics Primary Hyperoxaluria Panel
    Primary Hyperoxaluria Panel Test code: KI0801 Is a 3 gene panel that includes assessment of non-coding variants. Is ideal for patients with a clinical suspicion of hyperoxaluria. About Primary Hyperoxaluria The primary hyperoxalurias are rare disorders of glyoxylate metabolism, which result in markedly increased endogenous oxalate synthesis by the liver. They are characterized by an excess of oxalate resulting in manifestations ranging from occasional renal stones, recurrent nephrolithiasis and nephrocalcinosis to end-stage renal disease (ESRD) and systemic oxalosis. Presenting ranges from the neonatal period to adulthood. Among disorders causing hyperoxaluria, the primary hyperoxalurias are the most severe, ultimately leading to ESRD and if untreated, death in most patients. Type I primary hyperoxaluria (PH1), is caused by deficient or absent activity of liver-specific peroxisomal alanine glyoxylate aminotransferase (AGT). In some patients with PH1 type disease, the enzyme is present but mistargeted to mitochondria where it is metabolically inactive. The severe infantile form is characterized by a failure to thrive, nephrocalcinosis with or without nephrolithiasis and early ESRD. Onset in childhood and adolescence is often characterized by recurrent urolithiasis (with or without nephrocalcinosis) and progressive renal failure. The late onset form is characterized by occasional renal stones with onset in adulthood, but acute renal failure caused by bilateral obstruction of the kidneys by oxalate stones may occur. Other manifestations include urinary tract infections, dysuria and hematuria. The ongoing systemic oxalosis also may lead to other clinical manifestations such as cardiac conduction defects, vascular calcification with distal gangrene, disturbed vision, specific brown colored retinal deposits, skin nodules, joint involvement and bone disease leading to fractures in long-term dialysis-dependent patients.
    [Show full text]
  • Redalyc.The Nutritional Limitations of Plant-Based Beverages in Infancy
    Nutrición Hospitalaria ISSN: 0212-1611 [email protected] Sociedad Española de Nutrición Parenteral y Enteral España Vitoria, Isidro The nutritional limitations of plant-based beverages in infancy and childhood Nutrición Hospitalaria, vol. 34, núm. 5, 2017, pp. 1205-1214 Sociedad Española de Nutrición Parenteral y Enteral Madrid, España Available in: http://www.redalyc.org/articulo.oa?id=309253341026 How to cite Complete issue Scientific Information System More information about this article Network of Scientific Journals from Latin America, the Caribbean, Spain and Portugal Journal's homepage in redalyc.org Non-profit academic project, developed under the open access initiative Nutr Hosp. 2017; 34(5):1205-1214 ISSN 0212-1611 - CODEN NUHOEQ S.V.R. 318 Nutrición Hospitalaria Revisión The nutritional limitations of plant-based beverages in infancy and childhood Limitaciones nutricionales de las bebidas vegetales en la lactancia y la infancia Isidro Vitoria Unit of Nutrition and Metabolopathies. Hospital Universitario y Politécnico La Fe. Valencia, Spain Abstract Breastfeeding, infant formula and cow’s milk are basic foods in infant nutrition. However, they are being increasingly replaced either totally or partially by plant-based beverages. The composition of 164 plant-based beverages available in Spain was reviewed based on the nutritional labeling of the package and the man- ufacturers’ webpages. This was compared to the composition of cow’s milk and infant formula. In addition, the nutritional disease associated with consumption of plant-based beverages in infants and children was reviewed by means of a literature search in Medline and Embase since 1990 based on the key words “plant-based beverages” or “rice beverages” or “almond beverages” or “soy beverages” and “infant” or “child”.
    [Show full text]
  • Molecular Analysis of the Aldolase B Gene in Patients with Hereditary
    1of8 J Med Genet: first published as 10.1136/jmg.39.9.e56 on 1 September 2002. Downloaded from ONLINE MUTATION REPORT Molecular analysis of the aldolase B gene in patients with hereditary fructose intolerance from Spain J C Sánchez-Gutiérrez, T Benlloch, M A Leal, B Samper, I García-Ripoll, J E Felíu ............................................................................................................................. J Med Genet 2002;39:e56 (http://www.jmedgenet.com/cgi/content/full/39/9/e56) ereditary fructose intolerance (HFI) is an autosomal resident in the following regions: Madrid (11 families), Anda- recessive metabolic disorder caused by aldolase (fructo- lusia (4), Galicia (3), Estremadura (1), Valencia (1), and Hsediphosphate aldolase, EC 4.1.2.13) B deficiency.1 The Spanish possessions in North Africa (1). HFI diagnosis was B isoform of aldolase is critical for the metabolism of based on enzymatic studies (deficient aldolase B activity in exogenous fructose by the liver, kidney, and intestine, since it hepatic biopsies from 16 patients) or clinical symptoms (six can use fructose-1-phosphate as substrate at physiological patients). Another six subjects were suspected to suffer from concentrations, unlike aldolases A and C. Affected subjects HFI on the basis of dietary intolerance with episodes sugges- suffer abdominal pain, vomiting, and hypoglycaemia after the tive of hypoglycaemia and occurrence of the disease in their ingestion of fructose, sucrose, or sorbitol. Continued ingestion first degree relatives. of noxious sugars causes hepatic and renal injury, which eventually leads to liver cirrhosis and sometimes death, Reagents particularly in small infants.1 Treatment consists of strict Thermostable DNA polymerase, deoxynucleotides, and gen- elimination of fructose, sucrose, and sorbitol from the diet eral PCR products were from Biotools (Madrid, Spain).
    [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]
  • 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]
  • Open Full Page
    Research Article Glutathione Transferase P Plays a Critical Role in the Development of Lung Carcinogenesis following Exposure to Tobacco-Related Carcinogens and Urethane Kenneth J. Ritchie,1 Colin J. Henderson,1 Xiu Jun Wang,1 Olga Vassieva,1 Dianne Carrie,1 Peter B. Farmer,2 Margaret Gaskell,2 Kevin Park,3 and C. Roland Wolf1 1Cancer Research UK Molecular Pharmacology Unit, Biomedical Research Centre, Ninewells Hospital and Medical School, Dundee, United Kingdom; 2Cancer Biomarkers and Prevention Group, Biocentre, University of Leicester, Leicester, United Kingdom;and 3Department of Pharmacology and Therapeutics, University of Liverpool, Liverpool, United Kingdom Abstract family of dimeric enzymes (EC 2.5.1.18;GST a, A, k, u, j, ~, n, and N) Human cancer is controlled by a complex interaction between identified on the basis of their amino acid sequence and substrate genetic and environmental factors. Such environmental specificity (4). GSTs are regarded as being important detoxification factors are well defined for smoking-induced lung cancer; enzymes due to their capacity to catalyze the addition of reduced however, the roles of specific genes have still to be elucidated. glutathione (GSH) to reactive electrophiles produced by cyto- Glutathione transferase P (GSTP) catalyzes the detoxification chrome P450 metabolism. As a consequence, there has been a of electrophilic diol epoxides produced by the metabolism of significant interest in elucidating the relationship between GSTP polycyclic aromatic hydrocarbons such as benzo[a]pyrene function and resistance to cancer chemotherapeutic agents and the development of cancer (5–7). In a genetic approach to study GST (BaP), a common constituent of tobacco smoke. Activity- altering polymorphisms in Gstp have therefore been speculated functions, we have generated mice nulled at the Gstp gene locus to be potential risk modifiers in lung cancer development.
    [Show full text]
  • Biochemistry Entry of Fructose and Galactose
    Paper : 04 Metabolism of carbohydrates Module : 06 Entry of Fructose and Galactose Dr. Vijaya Khader Dr. MC Varadaraj Principal Investigator Dr.S.K.Khare,Professor IIT Delhi. Paper Coordinator Dr. Ramesh Kothari,Professor UGC-CAS Department of Biosciences Saurashtra University, Rajkot-5, Gujarat-INDIA Dr. S. P. Singh, Professor Content Reviewer UGC-CAS Department of Biosciences Saurashtra University, Rajkot-5, Gujarat-INDIA Dr. Charmy Kothari, Assistant Professor Content Writer Department of Biotechnology Christ College, Affiliated to Saurashtra University, Rajkot-5, Gujarat-INDIA 1 Metabolism of Carbohydrates Biochemistry Entry of Fructose and Galactose Description of Module Subject Name Biochemistry Paper Name 04 Metabolism of Carbohydrates Module Name/Title 06 Entry of Fructose and Galactose 2 Metabolism of Carbohydrates Biochemistry Entry of Fructose and Galactose METABOLISM OF FRUCTOSE Objectives 1. To study the major pathway of fructose metabolism 2. To study specialized pathways of fructose metabolism 3. To study metabolism of galactose 4. To study disorders of galactose metabolism 3 Metabolism of Carbohydrates Biochemistry Entry of Fructose and Galactose Introduction Sucrose disaccharide contains glucose and fructose as monomers. Sucrose can be utilized as a major source of energy. Sucrose includes sugar beets, sugar cane, sorghum, maple sugar pineapple, ripe fruits and honey Corn syrup is recognized as high fructose corn syrup which gives the impression that it is very rich in fructose content but the difference between the fructose content in sucrose and high fructose corn syrup is only 5-10%. HFCS is rich in fructose because the sucrose extracted from the corn syrup is treated with the enzyme that converts some glucose in fructose which makes it more sweet.
    [Show full text]