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).


"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 ... 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.

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.


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

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


"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

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

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


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

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.
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