Glucose-6-phosphate dehydrogenase (G6PD) deficiency

A forum investigating the similarities between COVID-19 and fluoride poisoning, thyroid dysfunction and Gq/11 pathways.
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Glucose-6-phosphate dehydrogenase (G6PD) deficiency

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Glucose-6-phosphate dehydrogenase (G6PD) deficiency
© 2020 PFPC

Glucose-6-phosphate dehydrogenase (G6PD) is the rate-limiting enzyme of the pentose phosphate pathway that modulates cellular redox homeostasis via the regeneration of NADPH.

G6PD deficiency is a disorder that most often affects males.

G6PD-deficient cells are highly susceptible to viral infection (Wu et al, 2015; Ho et al., 2008).
  • Wu YH, Chiu DT, Lin HR, Tang HY, Cheng ML, Ho HY - "Glucose-6-Phosphate Dehydrogenase Enhances Antiviral Response through Downregulation of NADPH Sensor HSCARG and Upregulation of NF-κB Signaling" Viruses 7(12):6689-706 (2015)
    doi: 10.3390/v7122966

    Ho HY, Cheng ML, Weng SF, Chang L, Yeh TT, Shih SR, Chiu DT - " Glucose-6-phosphate dehydrogenase deficiency enhances enterovirus 71 infection" J Gen Virol 89(Pt 9):2080-2089 (2008) doi: 10.1099/vir.0.2008/001404-0. PMID: 18753216.

COVID-19

"Since G6PD deficiency results in the redox imbalance in the erythrocytes leading to hemolysis and tissue damage as a result of insufficient oxygen transportation, COVID-19 might increase the mortality risk of patients with G6PD deficiency [2–5]." (Aydemir & Ulusu, 2020)

  • Aydemir D, Ulusu NN - "Is glucose-6-phosphate dehydrogenase enzyme deficiency a factor in Coronavirus-19 (COVID-19) infections and deaths?" Pathog Glob Health 114(3):109-110 (2020)
    doi: 10.1080/20477724.2020.1751388. Epub 2020 Apr 14. PMID: 32286926
    https://www.tandfonline.com/doi/full/10 ... 20.1751388

NOTE: COVID-19 patients are often treated with hydrochloroquine which, in turn, may cause serious side effects in such patients with G6PD deficiency (Kassi et al, 2020; Beauverd et al., 2020). Patients should be screened before treatment with hydrochloroquine.
  • Kassi EN, Papavassiliou KA, Papavassiliou AG - "G6PD and chloroquine: Selecting the treatment against SARS-CoV-2?" J Cell Mol Med 24(9):4913-4914 (2020) doi: 10.1111/jcmm.15312. Epub 2020 Apr 16. PMID: 32281268; PMCID: PMC7205832.

    Beauverd Y, Adam Y, Assouline B, Samii K - "COVID-19 infection and treatment with hydroxychloroquine cause severe haemolysis crisis in a patient with glucose-6-phosphate dehydrogenase deficiency" Eur J Haematol. 2020 Apr 23. doi: 10.1111/ejh.13432. Epub ahead of print. PMID: 32324284.
    https://pubmed.ncbi.nlm.nih.gov/32324284/

Fluoride

Fluoride may not only be worse for those with G6PD deficiency (Pornprasert et al., 2017), it has caused such G6PD deficiency in kidney tissue of rats (Thangapandiyan & Miltonprabu, 2014).
"Thus, the excessive fluoride consumption increased haematological alteration in subjects with iron deficiency, thalassaemia, and G-6-PD deficiency and that may increase the risk of anaemia in these subjects." (Pornprasert et al, 2017)
  • Pornprasert S, Wanachantararak P, Kantawong F, Chamnanprai S, Kongpan C, Pienthai N, Yanola J, Duangmano S, Prasannarong M - "Excessive fluoride consumption increases haematological alteration in subjects with iron deficiency, thalassaemia, and glucose-6-phosphate dehydrogenase (G-6-PD) deficiency" Environ Geochem Health 39(4):751-758 (2017)
    doi: 10.1007/s10653-016-9845-x. Epub 2016 Jun 18. PMID: 27318827
    https://pubmed.ncbi.nlm.nih.gov/27318827/
Thangapandiyan S, Miltonprabu S - "Epigallocatechin gallate supplementation protects against renal injury induced by fluoride intoxication in rats: Role of Nrf2/HO-1 signaling" Toxicol Rep 1:12-30 (2014) doi: 10.1016/j.toxrep.2014.01.002. PMID: 28962222; PMCID: PMC5598207
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5598207/


Gq/11

"Gq/11 activate multiple downstream signals, including PKC, ERK1/2, Raf, tyrosine kinases, receptor tyrosine kinases (EGFR, PDGF, insulin receptor), nuclear factor κB and reactive oxygen species (ROS)...AT1 receptor-mediated activation of NADPH oxidase releases ROS, resulting in the activation of pro-inflammatory transcription factors and stimulation of small G proteins such as Ras, Rac and RhoA". (Balakumar et al., 2014)

  • Balakumar P, Jagadeesh G - "A century old renin-angiotensin system still grows with endless possibilities: AT1 receptor signaling cascades in cardiovascular physiopathology" Cell Signal 26(10):2147-60 (2014) doi: 10.1016/j.cellsig.2014.06.011. Epub 2014 Jul 5. PMID: 25007996
    https://pubmed.ncbi.nlm.nih.gov/25007996

Yen WC, Wu YH, Wu CC, Lin HR, Stern A, Chen SH, Shu JC, Tsun-Yee Chiu D - " Impaired inflammasome activation and bacterial clearance in G6PD deficiency due to defective NOX/p38 MAPK/AP-1 redox signaling" Redox Biol 28:101363 (2020) doi: 10.1016/j.redox.2019.101363. Epub 2019 Nov 2. PMID: 31707353; PMCID: PMC6854078
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6854078/

Jain A, Anand-Srivastava MB - "Natriuretic peptide receptor-C-mediated attenuation of vascular smooth muscle cell hypertrophy involves Gqα/PLCβ1 proteins and ROS-associated signaling" Pharmacol Res Perspect 6(1):e00375 (2019) doi: 10.1002/prp2.375. PMID: 29417757; PMCID: PMC5817836
https://pubmed.ncbi.nlm.nih.gov/29417757/


Thyroid

Thyroid hormones modulate G6PD activity (Fritz & Kletzien, 1987; Miksicek & Towle, 1982).

Fritz RS, Kletzien RF - "Regulation of glucose-6-phosphate dehydrogenase by diet and thyroid hormone" Mol Cell Endocrinol 51(1-2):13‐17 (1987) doi:10.1016/0303-7207(87)90113-4

Miksicek RJ, Towle HC - "Changes in the rates of synthesis and messenger RNA levels of hepatic glucose-6-phosphate and 6-phosphogluconate dehydrogenases following induction by diet or thyroid hormone" J Biol Chem 257(19):11829-35 (1982) PMID: 6181061


Thyroid and Age

"“While glucose-6-phosphate dehydrogenase activity levels did not change in heart, brain and liver tissues of 30-day-old rats, they increased in brain and heart tissues of 60-day-old experimental groups, but decreased in the liver. Catalase activities decreased in the liver and heart of rats with hypothyroidism, but increased in erythrocytes.” (Yilmaz et al., 2003)

  • Yilmaz S, Ozan S, Benzer F, Canatan H - “Oxidative damage and antioxidant enzyme activities in experimental hypothyroidism” Cell Biochem Funct. 21(4):325-30 (2003)
SEE also:

NF-kappaB. viewtopic.php?f=66&t=1888&p=1946&hilit=NADPH#p1946
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