Galactosemia : A Genetic Disease of Leloir Pathway

Authors

  • Sikander Ali  Institute of Industrial Biotechnology (IIB), GC University Lahore, Pakistan
  • Rabia Iqbal Khan  Institute of Industrial Biotechnology (IIB), GC University Lahore, Pakistan
  • Almas Azhar  Institute of Industrial Biotechnology (IIB), GC University Lahore, Pakistan

Keywords:

Galactosemia, Leloir pathway, galactokinase (GALK), UDP-galactose-4-epimerase (GALE), Galactose-1-phosphate uridylyl transferase (GALT)

Abstract

Galactosemia is a genetic disorder which causes inability to metabolize galactose in the body. Our body converts galactose into glycolytic intermediate by Leloir pathway. Galactosemia is caused by the mutation in the gene encoding enzymes of Leloir pathway or non-functioning of these enzymes. Types of galactosemia are due to different enzyme deficiencies. Type I is for GALT (galactose-1-phosphate uridylyl transferases) enzyme deficiency, type II is for GALK (galactose kinase) and type III is for GALE (uridine-diphosphate galactose-4-epimerase) deficiency in the body. Structural alterations in the enzyme conformation, due to defective gene, cause loss of enzyme activity by disrupting enzyme active site. These cause accumulation of galactose and its derivatives causing many problems like cataracts, brain damage and liver damage etc. Their symptoms appear like low weight, jaundice, vomiting etc. This disease is diagnosed via number of test like genetic test, blood test, urine test, new born screening etc. For treatment of galactosemia, strict diet plan is recommended to patients containing galactose free diet such as fermented food etc. Research related to drug treatment is the scope in galactosemia.

References

  1. Ballard FJ. Kinetic studies with liver galactokinase. Biochem. J. 1996; 101: 70-75.
  2. Beerens Koen WS. UDP-hexose 4-epimerases: a view on structure, mechanism and substrate specificity, Carbohydr. Res. 2015;414: 8-14.
  3. Berry GT, Walter JH, Saudubray JM, den Berghe G. Disorders of galactose metabolism, Inborn Metabolic Diseases: Diagnosis and Treatment (Eds.) New York, NY: Springer; 2012; chap 7.
  4. Berry GT. Galactosemia: When is it a newborn screening emergency? Mol. Genet, Metab. 2012;106: 7-11.
  5. Berry GT. The rate of de novo galactose synthesis in patients of galactose-1-phosphate uridylyl transferases deficiency, Mol. Genet. Metab. 2004; 81: 22-30.
  6. Bertoli DA. 1966. Developmental aspects and some characteristics of mammalian galactose-1-phosphate uridylyl transferase, J. Biol. Chem. 1996; 241:4023-4029.
  7. Beutler E, Glactosemia: Screening and diagnosis, Clinical Biochem. 1991; 24: 293-300.
  8. Bosch AM, Bakker HD, Gennip AH, Kempen JV, Wanders RJ , Wijburg FA. Clinical features of galactokinase deficiency: a review of the literature, J. Inherit. Metab. Dis. 2002;25: 629-634.
  9. Bosch AM. Classical galactosemia revisited, J. Inh. Meta. Dis. 2006; 29: 516-525.
  10. Calcar C, Bernstein LE, Rohr FJ, Scaman CH, Yannicelli S, Berry GT. A re-evaluation of life-long severe galactose restriction for the nutrition management of classic galactosemia, Mol. Genet. Metab. 2014; 112: 191-197.
  11. Davit-Spraul AM, Pourci L, Soni T, Lemonnier A. Metabolic effects of galactose on human HepG2 hepatoblastoma cells, Metab. 1994; 43: 945-952.
  12. Demendi Melinda, Ishiyama N, Lam JS, Berghuis AM, Creuzenet C. Towards a better understanding of the substrate specificity of the UDP-N-acetyl glucosamine C4 epimerase, WbpP. Biochem. J.2005; 389: 173-80.
  13. Dey PM, Campillo ED. Biochemistry of the multiple forms of glycosidase in plants, Adv. Enz. Rela. Mol. Biol. 2006; 56: 141-249.
  14. Elzouki YA, Harfi HA, Nazer H. Textbook of clinical pediatrics, 2nd edition, Springer-Verlag Berlin Heidelberg, 2012.
  15. Frey PA. The Leloir pathway: a mechanistic imperative for three enzymes to change the stereochemical configuration of a single carbon in galactose, FASEB.J. 1996;10: 461-470.
  16. Fridovich-Keil J, Walter JH. Galactosemia. In: Valle, D. (Ed, Online metabolic and molecular basis of disease. McGraw-Hill, 2008.
  17. Goppert F. Galactosuria after lactation in congenital familial chronic liver disease, Clinical web. 1917;54: 473-477.
  18. Gross PB. Hidden sources of galactose in the environment, Eur. J. Pedia. 1995; 154: 87-92
  19. Haldeman-Englert, Zieve CD, Ogilvie I. Galactosemia. 2015.
  20. Harris JC, developmental neuropsychiatry: assessment, diagnosis and treatment of developmental disorders, volume II. New York: oxford university press. 1998.
  21. Hartnett CH, Kim CH, Scaman. Effect of processing on galactose in selected fruits, Canad. J. Diet. Pract. Res. 2007; 68: 46-50.
  22. Holde HM, Thodena JB, Timson DJ and Reecec RJ. Galactokinase: structure, function and role in type II galactosemia, CMLS, Cell. Mol. Life Sci. 2004; 61: 2471-2484.
  23. Holden HM, Ivan R, James B, Thoden. Structure and function of enzymes of Leloir pathway for galactose metabolism, J. Biol. Chem. 2003; 278: 43885-43888.
  24. Hongjie Guo LL. Biochemical Characterization of UDP-GlcNAc/Glc 4-Epimerase from Escherichia coli O86:B7?, Biochem. 2006; 47: 13760-13768.
  25. Isselbacher KJ, Anderson EP, Kurahashi E and Kalckar HM. Congenital Galactosemia: a Single Enzymatic Block in Galactose Metabolism, Sci. 1956; 123: 635-636.
  26. Johnson LD. Galactose-1-phosphate uridylyltransferase activity in chronic lymphosytic leukeamia, Cancer. Biochem. Biophys. 1979; 3: 75-79.
  27. Leloir L. The enzymatic transformation of uridine-diphosphate glucose into a galactose derivative, Arc. Biochem. Biophys. 1951; 33(2): 186-190.
  28. Lesk AM NAD-binding domains of dehydrogenases, Curr. Opin. Struct. Biol. 1995 5; 775-783.
  29. Leslie NY, Yager C, Reynolds R, Segal S. UDP-galactosepyrophosphorylase in mice with galactose-1-phosphate uridyltransferase, Mol. Genet. Metab. 2005; 85: 21-27.
  30. Liu Y, Thoden JB, Kim J, Berger E, Gulick AM, Ruzicka FJ, Holden HM, Frey PA. Mechanistic roles of tyrosine 149 and serine 124 in UDP-galactose 4-epimerase from Escherichia coli, Biochem. 1997; 36: 10675?10684.
  31. Mason HH and Turner ME. Report of case with studies on carbohydrates, Amer. J. Dis. Child.1935; 50: 359-374.
  32. McCorvie TJ, Timson DJ. The Structural and Molecular Biology of Type I Galactosemia: Enzymology of galactose-1-phosphate uridylyl transferase. IUBMB Life. 2011; 694-700.
  33. Openo KK, Schulz JM, Vargas CA, Orton CS, Epstein MP, Schnur RE, Scaglia F, Berry GT, Gottesman GS, Ficicioglu C, Slonim AE, Schroer RJ, Yu C, Rangel VE, Keenan J, Lamance K Fridovich-Kei JL l. Epimerase-deficiency galactosemia is not a binary condition, Amer. J. Hum. Genet. 2006;78: 89-102.
  34. Petry K, Greinix HT, Nudelman E, Eisen H, Hakomori S, Levy HL, Reichardt JK. Characterization of a novel biochemical abnormality in galactosemia: Deficiency of glycolipids containing galactose or N-acetylgalactosamine and accumulation of precursors in brain and lymphocytes, Biochem. Med. Metab. Biol. 1991; 46: 93-104.
  35. Sega S. Rogers S. Nucleotide inhibition of mammalian liver galactose-1-phosphate uridylyl transferase, Biochemica et biophysica Acta. 1971;250: 351-360.
  36. Slepak TI. Involvement of endoplasmic reticulum stress in a novel classic galactosemia model, Mol. Genet. Metab. 2007; 78-87.
  37. Tang M, Odejinm SIi, Vankayalapati H, Wierenga KJ and Lai K. Innovative therapy for classic galacctosemia- Tale of two HTS, Mol. Genet. Metab. 2012; 105: 22-30.
  38. Tang MW. Molecular and biochemical characterization of human galactokinase and its small molecule inhibitors, Chemico biol interact. 2010; 376-378.
  39. Timson D. The structural and molecular biology of type III galactosemia, IUBMB life. 2006; 83-89.
  40. Voet D, Voet JG. Biochemistry 4th edition . Kaye pace 1990;631-633.
  41. Wierenga KJ. Highthroughput screening for human galactokinase inhibitors, J. Biomol. Screen. 2008; 415-423.
  42. Wolfrom ML. The Raffinose family of oligosaccharides, Adv. Carbohydr. Chem. 1954; 149-185.

International Journal of Scientific Research in Science and Technology

Downloads

Published

2017-06-30

Issue

Volume 3, Issue 4, May-June-2017

Section

Research Articles

License

Copyright (c) IJSRST

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

How to Cite

[1]
Sikander Ali, Rabia Iqbal Khan, Almas Azhar, " Galactosemia : A Genetic Disease of Leloir Pathway, International Journal of Scientific Research in Science and Technology(IJSRST), Online ISSN : 2395-602X, Print ISSN : 2395-6011, Volume 3, Issue 4, pp.389-397, May-June-2017.