The Possible Role of The Glucose-6-Phosphate Dehydrogenase Enzyme Deficiency in The Polyneuropathies

Abstract

Glucose is the main energy source of the various types of cells and largely metabolized by either glycolysis or pentose phosphate pathway PPP . Glucose-6-phosphate dehydrogenase G6PD, glucose 6-phosphate G6P : NADP + oxidoreductase, EC 1.1.1.49 is the first and rate limiting enzyme of the oxidative branch of the PPP. This enzyme found in many species from bacteria to humans and is found in all cell types. G6PD deficiency is the most common enzyme deficiency affecting 400 million people worldwide. However, moderate G6PD deficiency may not give symptoms but can lead to various neurological and neurodegenerative disorders including polyneuropathies. Both inflammation and oxidative stress play a major role in the formation of the neurological disorders, however, G6PD gives advantage to brain and nerve cells to fight against oxidative stress, neurodegeneration, neuronal survival and aging. In conclusion, G6PD plays vital role to maintain homeostasis of lipid, redox and energy metabolisms. Thus, impairment in the G6PD activity may cause elevated levels of oxidative stress involved in the formation of the neurodegeneration and may involve in the primary cause of idiopathic sensory-motor polyneuropathy

Keywords

• Glucose-6-phosphate dehydrogenase,oxidative stress,brain, glucose metabolism

References

1. . Erbsloh F, Bernsmeier A, Hillesheim H. The glucose consumption of the brain & its dependence on the liver. Arch Psychiatr Nervenkr Z Gesamte Neurol Psychiatr 1958;196:611–626. [CrossRef]
2. 2. Howarth C, Gleeson P, Attwell D. Updated energy budgets for neural computation in the neocortex and cerebellum. J Cereb Blood Flow Metab 2012;32:1222–1232. [CrossRef]
3. 3. Mergenthaler P, Lindauer U, Dienel GA, Meisel A. Sugar for the brain: the role of glucose in physiological and pathological brain function. Trends Neurosci 2013;36:587–597. [CrossRef]
4. 4. Raichle ME, Gusnard DA. Appraising the brain’s energy budget. Proc Natl Acad Sci U S A 2002;99:10237–10239. [CrossRef]
5. 5. Belanger M, Allaman I, Magistretti PJ. Brain energy metabolism: focus on astrocyte-neuron metabolic cooperation. Cell Metab 2011;14:724–738. [CrossRef]
6. 6. Ulusu NN, Gok M, Erman B, Turan B. Effects of Timolol Treatment on Pancreatic Antioxidant Enzymes in Streptozotocin-induced Diabetic Rats: An Experimental and Computational Study. J Med Biochem 2019;38:306–316. [CrossRef]
7. 7. Bouzier-Sore AK, Bolanos JP. Uncertainties in pentose-phosphate pathway flux assessment underestimate its contribution to neuronal glucose consumption: relevance for neurodegeneration and aging. Front Aging Neurosci 2015;7:89. [CrossRef]
8. 8. Amaral AI, Hadera MG, Tavares JM, Kotter MR, Sonnewald U. Characterization of glucose-related metabolic pathways in differentiated rat oligodendrocyte lineage cells. Glia 2016;64:21–34. [CrossRef]

9. 9. Ferris HA, Perry RJ, Moreira GV, Shulman GI, Horton JD, Kahn CR. Astrocyte cholesterol and whole-body metabolism. Proc Natl Acad Sci USA 2017;114:1189–1194. [CrossRef]
10. 10. Levy HR, Raineri RR, Nevaldine BH. On the structure and catalytic function of mammary glucose-6-phosphate dehydrogenase. J Biol Chem 1966;241:2181–2187. https://www.jbc.org/ content/241/10/2181.long
11. 11. Nkhoma ET, Poole C, Vannappagari V, Hall SA, Beutler E. The global prevalence of glucose-6-phosphate dehydrogenase deficiency: a systematic review and meta-analysis. Blood Cells Mol Dis 2009;42:267–278. [CrossRef]
12. 12. Luzzatto L, Nannelli C, Notaro R. Glucose-6-Phosphate Dehydrogenase Deficiency. Hematol Oncol Clin North Am 2016;30:373–393. [CrossRef]
13. 13. Bensaad K, Tsuruta A, Selak MA, et al. TIGAR a p53-inducible regulator of glycolysis and apoptosis. Cell 2006;126:107–120. [CrossRef]
14. 14. Zhang HS, Wang SQ. Nrf2 is involved in the effect of tanshinone IIA on intracellular redox status in human aortic smooth muscle cells. Biochem Pharmacol 2007;73:1358–1366. [CrossRef]
15. 15. Bao BY, Ting HJ, Hsu JW, Lee YF. Protective role of 1 alpha, 25-dihydroxyvitamin D3 against oxidative stress in nonmalignant human prostate epithelial cells. Int J Cancer 2008;122:2699–2706. [CrossRef]
16. 16. Pan S, World CJ, Kovacs CJ, Berk BC. Glucose 6-phosphate dehydrogenase is regulated through c-Src-mediated tyrosine phosphorylation in endothelial cells. Arterioscler Thromb Vasc Biol 2009;29:895–901. [CrossRef]
17. 17. Duvel K, Yecies JL, Menon S, et al. Activation of a metabolic gene regulatory network downstream of mTOR complex 1. Mol Cell 2010;39:171–183. [CrossRef]
18. 18. Cosentino C, Grieco D, Costanzo V. ATM activates the pentose phosphate pathway promoting anti-oxidant defence and DNA repair. EMBO J 2011;30:546–555. [CrossRef]
19. 19. Jiang P, Du W, Wang X, et al. p53 regulates biosynthesis through direct inactivation of glucose-6-phosphate dehydrogenase. Nat Cell Biol 2011;13:310–316. [CrossRef]
20. 20. Stanton RC. Glucose-6-phosphate dehydrogenase, NADPH, and cell survival. IUBMB Life 2012;64:362–369. [CrossRef]
21. 21. Ho HY, Cheng ML, Chiu DT. Glucose-6-phosphate dehydrogenase-- beyond the realm of red cell biology. Free Radic Res 2014;48:1028– 1048. [CrossRef]
22. 22. Ulusu NN, Kus MS, Acan NL, Tezcan EF. A rapid method for the purification of glucose-6-phosphate dehydrogenase from bovine lens. Int J Biochem Cell Biol 1999;31:787–796. [CrossRef]
23. 23. Tandogan B, Ulusu NN. Purification and kinetics of bovine kidney cortex glutathione reductase. Protein Pept Lett 2010;17:667–674. [CrossRef]
24. 24. Tandogan B, Sengezer C, Ulusu NN. In Vitro Effects of Imatinib on Glucose-6-phosphate dehydrogenase and glutathione reductase. Folia Biol (Praha) 2011;57:57–64. https://fb.cuni.cz/file/5574/ FB2011A0010.pdf
25. 25. Tandogan B, Kuruüzüm-Uz A, Sengezer C, Güvenalp Z, Demirezer LÖ, Ulusu NN. In vitro effects of rosmarinic acid on glutathione reductase and glucose 6-phosphate dehydrogenase. Pharm Biol 2011;49:587– 594. [CrossRef]
26. 26. Ulusu NN. Glucose-6-phosphate dehydrogenase deficiency and Alzheimer’s disease: Partners in crime? The hypothesis. Med Hypotheses 2015;85:219–223. [CrossRef]
27. 27. Ulusu NN, Şengezer C. Kinetic mechanism and some properties of glucose-6-phosphate dehydrogenase from sheep brain cortex. Turk J Biochem 2012;37:340–347. [CrossRef]
28. 28. Aydemir D, Hashemkhani M, Durmusoglu EG, Acar HY, Ulusu NN. A new substrate for glutathione reductase: Glutathione coated Ag2S quantum dots. Talanta 2019;1:501–506. [CrossRef]
29. 29. Tang HY, Ho HY, Wu PR, et al. Inability to maintain GSH pool in G6PDdeficient red cells causes futile AMPK activation and irreversible metabolic disturbance. Antioxid Redox Signal 2015;22:744–759. [CrossRef]
30. 30. Aydemir D, Hashemkhani M, Acar HY, Ulusu NN. In vitro interaction of glutathione S-transferase-pi enzyme with glutathione-coated silver sulfide quantum dots: A novel method for biodetection of glutathione S-transferase enzyme. Chem Biol Drug Des 2019;94:2094–2102. [CrossRef]
31. 31. Aydemir D, Ulusu NN. Comment on the: Molecular mechanism of CAT and SOD activity change under MPA-CdTe quantum dots induced oxidative stress in the mouse primary hepatocytes. Spectrochim Acta A Mol Biomol Spectrosc 2020;220:117104. [CrossRef]
32. 32. Aydemir D, Sarayloo E, Ulusu NN. Rosiglitazone-induced changes in the oxidative stress metabolism and fatty acid composition in relation with trace element status in the primary adipocytes. J Medical Biochem 2019. [CrossRef]
33. 33. Aydemir D, Oztasci B, Barlas N, Ulusu NN Effects of the butylparaben on the glutathione-dependent and -independent antioxidant enzyme metabolisms. Arh Hig Rada Toksikol 2019;70:315–324. [CrossRef]
34. 34. Aydemir D, Karabulut G, Gok M, Barlas N, Ulusu NN. Data the DEHP induced changes on the trace element and mineral levels in the brain and testis tissues of rats. Data in Brief 2019;17:104526. [CrossRef]
35. 35. Aydemir D, Karabulut G, Gok M, Şimşek G, Barlas N, Ulusu NN. Impact of the Di(2-Ethylhexyl) Phthalate Administration on Trace Element and Mineral Levels in Relation of Kidney and Liver Damage in Rats. Biol Trace Elem Res 2018;186:474–488. [CrossRef]
36. 36. Zuo L, Hemmelgarn BT, Chuang CC, Best TM. The role of oxidative stress-induced epigenetic alterations in amyloid-β production in Alzheimer’s Disease. Oxid Med Cell Longev 2015;2015:604658. [CrossRef]
37. 37. Porter TD. Electron Transfer Pathways in Cholesterol Synthesis. Lipids 2015;50:927–936. [CrossRef]
38. 38. Dringen R. Metabolism and functions of glutathione in brain. Prog Neurobiol 2000;62:649–671. [CrossRef]
39. 39. Li M, Sun M, Cao L, et al. TIGAR-Regulated Metabolic Pathway Is Critical for Protection of Brain Ischemia. J Neurosci 2014;34:7458– 7471. [CrossRef]
40. 40. Cao L, Zhang D, Chen J, et al. G6PD plays a neuroprotective role in brain ischemia through promoting pentose phosphate pathway. Free Radic Biol Med 2017;112:433–444. [CrossRef]
41. 41. Emeritt J, Edeas M, Bricaire F. Neurodegenerative diseases and oxidative stress. Biomed Pharmacother 2004;58:39–46. [CrossRef]
42. 42. Evlice A, Ulusu NN. Glucose-6-phosphate dehydrogenase a novel hope on a blood-based diagnosis of Alzheimer’s disease. Acta Neurol Belg 2017;117:229–234. [CrossRef]
43. 43. Tiwari M. Glucose 6 phosphatase dehydrogenase (G6PD) and neurodegenerative disorders: Mapping diagnostic and therapeutic opportunities. Genes Dis 2017;4:196–203. [CrossRef]
44. 44. Salim S. Oxidative Stress and the central nervous system. J Pharmacol Exp Ther 2017;360:201–205. [CrossRef]
45. 45. Halliwell B. Oxidative stress and neurodegeneration: where are we now? J Neurochem 2006;97:1634–1658. [CrossRef]
46. 46. Bentsen H. Dietary polyunsaturated fatty acids, brain function and mental health. Microb Ecol Health Dis 2017;28:1281916. [CrossRef]
47. 47. Sofic E, Lange KW, Jellinger K, Riederer P. Reduced and oxidized glutathione in the substantia nigra of patients with Parkinson’s disease. Neurosci Lett 1992;142:128–130. [CrossRef]
48. 48. Sian J, Dexter DT, Lees AJ, et al. Alterations in glutathione levels in Parkinson’s disease and other neurodegenerative disorders affecting basal ganglia. Ann Neurol 1994;36:348–355. [CrossRef]
49. 49. Bains JS, Shaw CA. Neurodegenerative disorders in humans: the role of glutathione in oxidative stress-mediated neuronal death. Brain Res Brain Res Rev 1997;25:335–358. [CrossRef]
50. 50. Cadet JL, Brannock C. Free radicals and the pathobiology of brain dopamine systems. Neurochem Int 1998;32:117–131. [CrossRef]
51. 51. Arranz MJ, de Leon, J. Pharmacogenetics and pharmacogenomics of schizophrenia: a review of last decade of research. Mol Psychiatry 2007;12:707–747. [CrossRef]
52. 52. Bouayed J, Rammal H, Younos C, Soulimani R. Positive correlation between peripheral blood granulocyte oxidative status and level of anxiety in mice. Eur J Pharmacol 2007;564:146–9. [CrossRef]
53. 53. Bouayed J, Rammal M, Soulimani R. Oxidative stress and anxiety Relationship and cellular pathways. Oxid Med Cell Longev 2009;2:63– 67. [CrossRef]
54. 54. Masood A, Nadeem A, Mustafa SJ, O’Donnell M. Reversal of oxidative stress-induced anxiety by inhibition of phosphodiesterase-2 in mice. J Pharmacol Exp Ther 2008;326:369–379. [CrossRef]
55. 55. Tobe EH. Mitochondrial dysfunction, oxidative stress, and major depressive disorder. Neuropsychiatr Dis Treat 2013;9:567–573. [CrossRef]
56. 56. Vinik A, Casellini C, Nevoret ML. Diabetic Neuropathies. In: Feingold KR, Anawalt B, Boyce A, et al., editors. Endotext (Internet). South Dartmouth (MA): MDText. com, Inc.; 2000.
57. 57. Eziokwu AS, Angelini D. New Diagnosis of G6PD Deficiency Presenting as Severe Rhabdomyolysis. Cureus 2018;10:e2387. [CrossRef]
58. 58. Ozdemir S, Tandogan B, Ulusu NN, Turan B. Angiotensin II receptor blockage prevents diabetes-induced oxidative damage in rat heart. Folia Biol (Praha) 2009;55:11–16. https://fb.cuni.cz/Data/files/folia_ biologica/volume_55_2009_1/fb2009A0003.pdf
59. 59. West IC. Radicals and oxidative stress in diabetes. Diabet Med 2000;17:171–180. [CrossRef]
60. 60. Zhang Z, Liew CW, Handy DE, et al. High glucose inhibits glucose-6- phosphate dehydrogenase, leading to increased oxidative stress and β-cell apoptosis. FASEB J 2010;24:1497–1505. [CrossRef]
61. 61. Gokturk H, Ulusu NN, Gok M. Tuncay E, Can B, Turan B. Long-term treatment with a beta-blocker timolol attenuates renal-damage in diabetic rats via enhancing kidney antioxidant-defense system. Mol Cell Biochem 2014;395:177–186. [CrossRef]
62. 62. Mallet M, Hadjivassiliou M, Sarrigiannis PG, Zis P. The Role of Oxidative Stress in Peripheral Neuropathy. J Mol Neurosci 2020;70:1009–1017. [CrossRef]
63. 63. Pinna A, Solinas G, Masia C, Zinellu A, Carru C, Carta A. Glucose6-Phosphate Dehydrogenase (G6PD) Deficiency in Nonarteritic Anterior Ischemic Optic Neuropathy in a Sardinian Population, Italy. Invest Ophthalmol Vis Sci 2008;49:1328–1332. [CrossRef]
64. 64. Aydemir D, Ulusu NN. Is glucose-6-phosphate dehydrogenase enzyme deficiency a factor in Coronavirus-19 (COVID-19) infections and deaths? Pathogens and Global Health 2020;114:109–110. [CrossRef]