Volume 4, Issue 3 (Aug 2019)                   JNFS 2019, 4(3): 206-217 | Back to browse issues page

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Ghasemzadeh N, Karimi-Nazari E, Yaghoubi F, Zarei S, Azadmanesh F, Sargazi S. Molybdenum Cofactor Biology and Disorders Related to Its Deficiency; A Review Study . JNFS. 2019; 4 (3) :206-217
URL: http://jnfs.ssu.ac.ir/article-1-278-en.html
Cellular and Molecular Research Center, Zahedan University of Medical Sciences, Zahedan, Iran.
Abstract:   (1405 Views)

Background: Molybden, as a vital and essential micronutrient is directly involved in the metabolism of other elements including carbon, sulfur, and nitrogen. Molybdenum alone is not biologically active unless it binds to specific cofactors. Except for the bacterial nitrogenase, which contains molybdenum-Iron complex, molybdenum cofactor (Moco) is considered as the bioactive component placed in active site regions of molybdenum-containing enzymes. This review aimed to discuss the biological mechanisms involved in molybdenum metabolism highlighting Molybdenum cofactor deficiencies. Methods: Articles indexed in Pubmed, Google Scholar, and Scopus databases were used to extract the required information. Results: Moco, as the cofactor of sulfite oxidase, xanthine dehydrogenase, aldehyde oxidase, and nitrite reductase plays a substantial role in maintaining normal body homeostasis and reactive oxygen species (ROS) production. Lack of Moco is found to be associated with many inborn genetic disorders, such as mental retardation, brain immaturity, nervous shocks, and neurodegenerative diseases. Conclusion: Moco insufficiency compromises normal human body metabolism since it is reported to regulate the metabolic pathways of other elements. Although in recent years, substitution- and gene-therapies have been introduced to restore the metabolic pathways of patients with MoCD type A and B, the definitive treatment for this type of inborn disease has still remained ill-defined. More investigations are needed to completely understand the underlying pathophysiology of molybdenum-related diseases.

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Type of article: review article | Subject: public specific
Received: 2018/10/1 | Accepted: 2018/02/26 | Published: 2019/08/1 | ePublished: 2019/08/1

1. Abbasalipourkabir R, et al. 2015. Toxicity of zinc oxide nanoparticles on adult male Wistar rats. Food and chemical toxicology. 84: 154-160.
2. Aguilar M, Cárdenas J & Fernández E 1992. Quantitation of molybdopterin oxidation product in wild-type and molybdenum cofactor deficient mutants of Chalamydomonas reinhardtii. Biochimica et Biophysica Acta. 1160 (3): 269-274.
3. Atwal PS & Scaglia F 2016. Molybdenum cofactor deficiency. Molecular Genetics and Metabolism. 117 (1): 1-4.
4. Badwey J, Robinson JM, Karnovsky MJ & Karnovsky ML 1981. Superoxide production by an unusual aldehyde oxidase in guinea pig granulocytes. Characterization and cytochemical localization. Journal of Biological Chemistry. 256 (7): 3479-3486.
5. Baxter I, et al. 2008. Variation in molybdenum content across broadly distributed populations of Arabidopsis thaliana is controlled by a mitochondrial molybdenum transporter (MOT1). Public Library of Science Genetics. 4 (2): e1000004.
6. Belaidi AA & Schwarz G 2013. Metal insertion into the molybdenum cofactor: product–substrate channelling demonstrates the functional origin of domain fusion in gephyrin. Biochemical Journal. 450 (1): 149-157.
7. Blasco F, et al. 1998. NarJ is a specific chaperone required for molybdenum cofactor assembly in nitrate reductase A of Escherichia coli. Molecular Microbiology. 28 (3): 435-447.
8. Bortels H 1930. Molybdän als Katalysator bei der biologischen Stickstoffbindung. Archives of Microbiology. 1 (1): 333-342.
9. Del Rizzo M, et al. 2013. Metabolic stroke in a late-onset form of isolated sulfite oxidase deficiency. Molecular Genetics and Metabolism. 108 (4): 263-266.
10. Dent C & Philpot G 1954. Xanthinuria: an inborn error (or deviation) of metabolism. Lancet. 263 (6804): 182-185.
11. Duran M, et al. 1978. Combined deficiency of xanthine oxidase and sulphite oxidase: a defect of molybdenum metabolism or transport? Journal of Inherited Metabolic Disease. 1 (4): 175-178.
12. Fräsdorf B, Radon C & Leimkühler S 2014. Characterization and interaction studies of two isoforms of the dual localized 3-mercaptopyruvate sulfurtransferase TUM1 from humans. Journal of Biological Chemistry. 289 (50): 34543-34556.
13. Hagen WR 2011. Cellular uptake of molybdenum and tungsten. Coordination Chemistry Reviews. 255 (9-10): 1117-1128.
14. Hänsch R, et al. 2006. Plant sulfite oxidase as novel producer of H2O2 combination of enzyme catalysis with a subsequent non-enzymatic reaction step. Journal of Biological Chemistry. 281 (10): 6884-6888.
15. Hille R 2002. Molybdenum enzymes containing the pyranopterin cofactor: an overview. Metal Ions in Biological Systems. 39: 187-226.
16. Huang D-Y, Furukawa A & Ichikawa Y 1999. Molecular Cloning of Retinal Oxidase/Aldehyde Oxidase cDNAs from Rabbit and Mouse Livers and Functional Expression of Recombinant Mouse Retinal Oxidase cDNA inEscherichia coli. Archives of Biochemistry and Biophysics. 364 (2): 264-272.
17. Ichida K, Yoshida M, Sakuma R & Hosoya T 1998. Two siblings with classical xanthinuria type 1: significance of allopurinol loading test. Internal Medicine. 37 (1): 77-82.
18. Kaiser WM & Huber SC 2001. Post‐translational regulation of nitrate reductase: mechanism, physiological relevance and environmental triggers. Journal of Experimental Botany. 52 (363): 1981-1989.
19. Kisker C, et al. 1997. Molecular basis of sulfite oxidase deficiency from the structure of sulfite oxidase. Journal of Experimental Botany. 91 (7): 973-983.
20. Kramer S, Hageman RV & Rajagopalan K 1984. In vitro reconstitution of nitrate reductase activity of the Neurospora crassa mutant nit-1: specific incorporation of molybdopterin. Archives of biochemistry and biophysics. 233 (2): 821-829.
21. Kurlemann G, Debus O & Schuierer G 1996. Dextrometorphan in molybdenum cofactor deficiency. European Journal of Pediatrics. 155 (5): 422-423.
22. Lee H-J, et al. 2002. Molybdenum cofactor-deficient mice resemble the phenotype of human patients. Human Molecular Genetics. 11 (26): 3309-3317.
23. Leimkühler S, Wuebbens MM & Rajagopalan K 2001. Characterization of Escherichia coli MoeB and its involvement in the activation of molybdopterin synthase for the biosynthesis of the molybdenum cofactor. Journal of Biological Chemistry. 276 (37): 34695-34701.
24. Lewis NJ, Hurt P, Sealy‐Lewis HM & Scazzocchio C 1978. The Genetic Control of the Molybdoflavoproteins in Aspergillus nidulans IV. A Comparison between Purine Hydroxylase I and II. European Journal of Biochemistry. 91 (1): 311-316.
25. Mendel RR 2007. Biology of the molybdenum cofactor. Journal of Experimental Botany. 58 (9): 2289-2296.
26. Mendel RR & Leimkühler S 2015. The biosynthesis of the molybdenum cofactors. Journal of Biological Inorganic Chemistry. 20 (2): 337-347.
27. Nowak K, et al. 2004. Peroxisomal localization of sulfite oxidase separates it from chloroplast-based sulfur assimilation. Plant Cell Phsiology. 45 (12): 1889-1894.
28. Parmeggiani B, et al. 2015. In vitro evidence that sulfite impairs glutamatergic neurotransmission and inhibits glutathione metabolism-related enzymes in rat cerebral cortex. International Journal of Developmental Neuroscience. 42: 68-75.
29. Pau R & Lawson DM 2002. Transport, homeostasis, regulation, and binding of molybdate and tungstate to proteins. Metal Ions in Biological Systems. 39: 31-74.
30. Paul BD, et al. 2014. Cystathionine γ-lyase deficiency mediates neurodegeneration in Huntington’s disease. Nature. 509 (7498): 96-100.
31. Rajagopalan K & Johnson J 1992. The pterin molybdenum cofactors. Journal of Biological Chemistry. 267 (15): 10199-10202.
32. Reiss J 2000. Genetics of molybdenum cofactor deficiency. Human Genetics. 106 (2): 157-163.
33. Reiss J 2016. Molybdenum Cofactor and Sulfite Oxidase Deficiency. Journal of Metabolomics. 6 (184): 2153-0769.
34. Reiss J & Johnson JL 2003. Mutations in the molybdenum cofactor biosynthetic genes MOCS1, MOCS2, and GEPH. Journal of Human Mutation. 21 (6): 569-576.
35. Rodríguez-Trelles F, Tarrío R & Ayala FJ 2003. Convergent neofunctionalization by positive Darwinian selection after ancient recurrent duplications of the xanthine dehydrogenase gene. Proceedings of the National Academy of Sciences of the United States of America. 100 (23): 13413-13417.
36. Sanders SA, Eisenthal R & Harrison R 1997. NADH oxidase activity of human xanthine oxidoreductase: generation of superoxide anion. European Journal of Biochemistry. 245 (3): 541-548.
37. Santamaria-Araujo JA, Wray V & Schwarz G 2012. Structure and stability of the molybdenum cofactor intermediate cyclic pyranopterin monophosphate. Journal of Biological Inorganic Chemistry. 17 (1): 113-122.
38. Schwahn BC, et al. 2015. Efficacy and safety of cyclic pyranopterin monophosphate substitution in severe molybdenum cofactor deficiency type A: a prospective cohort study. Lancet. 386 (10007): 1955-1963.
39. Schwarz G 2016. Molybdenum cofactor and human disease. Current Opinion in Chemical Biology. 31: 179-187.
40. Schwarz G, Mendel RR & Ribbe MW 2009. Molybdenum cofactors, enzymes and pathways. Nature. 460 (7257): 839-847.
41. Schwarz G, et al. 2004. Rescue of lethal molybdenum cofactor deficiency by a biosynthetic precursor from Escherichia coli. Human Molecular Genetics. 13 (12): 1249-1255.
42. Scriver CR, Beaudet A, Sly W & Valle D 2001. The Metabolic and Molecular Bases of Inherited. McGraw-Hill, EUA.
43. Shaw S & Jayatilleke E 1990. The role of aldehyde oxidase in ethanol-induced hepatic lipid peroxidation in the rat. Biochemical Journal. 268 (3): 579-583.
44. Tejada-Jiménez M, Galván A & Fernández E 2011. Algae and humans share a molybdate transporter. Proceedings of the National Academy of Sciences of the United States of America. 108 (16): 6420-6425.
45. Terao M, et al. 2000. Cloning of the cDNAs coding for two novel molybdo-flavoproteins showing high similarity with aldehyde oxidase and xanthine oxidoreductase. Journal of Biological Chemistry. 275 (39): 30690-30700.
46. Tomatsu H, et al. 2007. An Arabidopsis thaliana high-affinity molybdate transporter required for efficient uptake of molybdate from soil. Proceedings of the National Academy of Sciences of the United States of America. 104 (47): 18807-18812.
47. Trigiano RN & Gray DJ 2004. Plant development and biotechnology. CRC press.
48. Turnlund JR 2002. Molybdenum metabolism and requirements in humans. Metal Ions in Biological Systems. 39: 727-739.
49. Tyagarajan SK & Fritschy J-M 2014. Gephyrin: a master regulator of neuronal function? Nature Reviews. Neuroscience. 15 (3): 141-156.
50. Veldman A, et al. 2010. Successful treatment of molybdenum cofactor deficiency type A with cPMP. Pediatrics. peds. 2009-2192.
51. Warner CK & Finnerty V 1981. Molybdenum hydroxylases in Drosophila. Molecular and General Genetics 184 (1): 92-96.
52. Yesbergenova Z, et al. 2005. The plant Mo‐hydroxylases aldehyde oxidase and xanthine dehydrogenase have distinct reactive oxygen species signatures and are induced by drought and abscisic acid. Plant Journal. 42 (6): 862-876.
53. Zarei S, Moradi H, Asadi S, Aabbasalipourkabir R & Ziamajidi N 2017. Study of the effect of zinc oxide on enzymatic antioxidant activity in male rats. Pajouhan Scientific Journal. 15 (3): 29-35.
54. Zhang X, Vincent AS, Halliwell B & Wong KP 2004. A mechanism of sulfite neurotoxicity: direct inhibition of glutamate dehydrogenase. Journal of Biological Chemistry. 279 (41): 43035-43045.

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