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Gene Review

G6pd  -  glucose-6-phosphate dehydrogenase

Rattus norvegicus

Synonyms: G6PD, G6pdx, Glucose-6-phosphate 1-dehydrogenase
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Disease relevance of G6pdx

  • We studied the regulation of glucose-6-phosphate dehydrogenase (G6PD) gene expression by chronic hypoxia [1].
  • DENA followed by phenobarbital led to the early appearance of foci of cellular alteration (from wk 4), of nodules (from wk 13), and of hepatocellular carcinomas (from wk 26). gamma-GT activity was raised in most of these nodules and carcinomas, while G-6-PD activity was raised in only 3 of 9 nodules but in all 9 carcinomas examined [2].
  • Hearts isolated from rats treated 36 hr before with interleukin 1 (IL-1) had increased glucose-6-phosphate dehydrogenase (G6PD) activity and decreased hydrogen peroxide levels and injury after global ischemia (I, 20 min)/reperfusion (R, 40 min) compared with hearts from untreated rats [3].
  • Carvedilol, a beta-adrenergic blocker and vasodilator with alpha 1-blocking activity (0.5, prevented the NE-induced increase in cardiac G-6-PD activity, in functional parameters (heart rate, left ventricular systolic pressure, and left ventricular dP/dtmax), and in the heart weight/body weight ratio [4].
  • Histologically, hepatocellular carcinomas were significantly fewer and smaller in GGT-positive and G6PD-positive lesions in rats treated with cysteamine than in untreated rats [5].

Psychiatry related information on G6pdx

  • From these results, we conclude that LPS-mediated G6PD expression prevents GSH depletion due to nitric oxide and suggest that this phenomenon may be a contributing factor in the defense mechanisms that protect astrocytes against nitric oxide-mediated cell injury [6].
  • There was a linear relationship between G6PD activity and section thickness up to 14 microns and between G6PD activity and reaction time up to 5-6 min as demonstrated by kinetic and end-point measurements [7].

High impact information on G6pdx

  • Of the 11 nodules examined cytochemically, none was gamma-glutamyltransferase (gamma-GT) positive and 2 were positive to glucose-6-phosphate dehydrogenase (G-6-PD) under oxygen [2].
  • CONCLUSIONS: Neoplastic cells acquire a growth advantage by their capacity to synthesize cholesterol and obtain reduced nicotinamide adenine dinucleotide phosphate by the malic enzyme pathway when G6PD activity is inhibited by peroxisome proliferators [8].
  • Our results indicate that IL-1 pretreatment causes an early (6 hr after IL-1 treatment) myocardial PMN accumulation and most likely an H2O2-dependent oxidative stress, which contributes to late (36 hr after IL-1 treatment) increases in myocardial G6PD activity and decreases in I/R injury [3].
  • Depletion of circulating blood PMN by prior treatment with vinblastine prevented both early (from treatment 6 hr before study) IL-1-induced increases in myocardial PMN accumulation, H2O2 levels, and GSSG contents and late (from treatment 36 hr before study) increases in myocardial G6PD activity and protection against I/R [3].
  • This antibody does not affect the catalytic activity of the enzyme and shows crossreactivity with the palmitoyl CoA-inactivated G6PD [9].

Chemical compound and disease context of G6pdx


Biological context of G6pdx

  • In light of these results, we suggest that G6PD activation represents a novel role for peroxynitrite in neuroprotection against nitric oxide-mediated apoptosis [14].
  • Thus, arachidonic acid inhibits the insulin stimulation of G6PD mRNA accumulation by stimulating the p38 MAPK pathway, thereby inhibiting insulin signal transduction [15].
  • We found that in adult cardiomyocytes, G6PD activity is rapidly increased in response to cellular oxidative stress, with translocation of G6PD to the cell membrane [16].
  • Furthermore, inhibition of G6PD depletes cytosolic GSH levels and subsequently results in cardiomyocyte contractile dysfunction through dysregulation of calcium homeostasis [16].
  • Inhibition was not dependent on the presence of the G6PD polyadenylation signal and the 3'-untranslated region, but substitution with the SV40 poly(A) signal attenuated the inhibition by arachidonic acid [17].

Anatomical context of G6pdx

  • Incubating the hepatocytes with the p38 MAPK inhibitor, SB203580, blocked the arachidonic acid inhibition of G6PD mRNA accumulation [15].
  • Moreover, functional overexpression of the G6PD gene in stably transformed PC12 cells induced NADPH accumulation and offered remarkable resistance against nitric oxide-mediated apoptosis, whereas G6PD gene-targeted antisense inhibition depleted NADPH levels and exacerbated cellular vulnerability [14].
  • Numerous studies have demonstrated a decrease in glucose-6-phosphate dehydrogenase (G6PD) activity during aging in many cell types, including red blood cells, fibroblasts and lens cells [18].
  • These data suggest that G6PD activity in epithelium of SI and LI decreases with aging due to the accumulation of significant amounts of enzyme bound to cell organelles, a condition which makes it less active than the soluble enzyme [18].
  • Moreover, the intracellular activity of G6PD has been shown to be regulated by binding to cell organelles [18].

Associations of G6pdx with chemical compounds

  • In this study, we have provided evidence for a signaling pathway for the arachidonic acid inhibition of G6PD mRNA abundance [15].
  • In an attempt to elucidate the mechanism responsible for this PPP stimulation and neuroprotection, we found evidence consistent with both exogenous and endogenous peroxynitrite-mediated activation of glucose-6-phosphate dehydrogenase (G6PD), an enzyme that catalyzes the first rate-limiting step in the PPP [14].
  • This effect was accompanied by an increase in G6PD activity (1.74-fold) and in the rate of glucose oxidation through the PPP (6.32-fold) [6].
  • However, inhibition of G6PD activity by dehydroepiandrosterone (DHEA; 100 microM), which prevented LPS-mediated enhancements in PPP activity and NADPH concentrations, caused a 50% decrease in the GSH/GSSG ratio after 24-36 h and in GSH concentrations after 60 h of incubation [6].
  • Treatment of cultured rat astrocytes with lipopolysaccharide (LPS; 1 microg/ml) increased mRNA expression of glucose-6-phosphate dehydrogenase (G6PD), the rate-limiting step in the pentose phosphate pathway (PPP), in a time-dependent fashion (0-24 h) [6].

Other interactions of G6pdx

  • The insulin stimulation of G6PD involves the phosphoinositide 3-kinase (PI 3-kinase) pathway (Wagle, A., Jivraj, S., Garlock, G. L., and Stapleton, S. R. (1998) J. Biol. Chem. 273, 14968-14974) [15].
  • In conclusion, our data show that IL-1beta stimulated G6PD activity and expression level, providing NADPH that is required by iNOS for NO production in RINm5F cells [19].
  • Non-protein sulphhydryl (NPSH) content, glucose-6-phosphate dehydrogenase (G-6-PD) and glutathione peroxidase (GP) were all increased from days 5 to 15 [20].
  • There were no significant differences in the catalase and G-6-PD activities of SO2 group as compared with controls [21].
  • Compared with animals left with the dams to be weaned spontaneously to the maternal low fat diet (SWC group), the PWC rats showed early increases in the activities of liver glucose-6-phosphate dehydrogenase (G-6-PD) and malic enzyme (ME) [22].

Analytical, diagnostic and therapeutic context of G6pdx

  • Thus, the possibility still exists that starved fat-refed animals contain glucose-6-phosphate dehydrogenase (G6PD) enzyme protein in an inactivated form no longer detectable by either enzyme activity or immunoprecipitation [23].
  • Cells from both sites in organ culture show increased G6PD activity in response to exogenous PGI2, but their dose:responses differ in shape [24].
  • Decreases in CAT activity following denervation or injection of BTX or TTX were parallel to increases in G6PD activity observed under these conditions [25].
  • BTX, an agent known to block nerve impulse conduction and axonal transport increased G6PD activity to 155% and 163% of control by days 2 and 4 after injection [25].
  • Adrenalectomy prior to PMS withdrawal enhanced the decline in MAD while sharply elevating G6PD and 20alpha-hydroxysteroid dehydrogenase [26].


  1. Induction of the glucose-6-phosphate dehydrogenase gene expression by chronic hypoxia in PC12 cells. Gao, L., Mejías, R., Echevarría, M., López-Barneo, J. FEBS Lett. (2004) [Pubmed]
  2. Hepatic foci of cellular and enzymatic alteration and nodules in rats treated with clofibrate or diethylnitrosamine followed by phenobarbital: their rate of onset and their reversibility. Greaves, P., Irisarri, E., Monro, A.M. J. Natl. Cancer Inst. (1986) [Pubmed]
  3. Interleukin 1 pretreatment decreases ischemia/reperfusion injury. Brown, J.M., White, C.W., Terada, L.S., Grosso, M.A., Shanley, P.F., Mulvin, D.W., Banerjee, A., Whitman, G.J., Harken, A.H., Repine, J.E. Proc. Natl. Acad. Sci. U.S.A. (1990) [Pubmed]
  4. Effects of norepinephrine on the oxidative pentose phosphate pathway in the rat heart. Zimmer, H.G., Lankat-Buttgereit, B., Kolbeck-Rühmkorff, C., Nagano, T., Zierhut, W. Circ. Res. (1992) [Pubmed]
  5. Inhibition by cysteamine of hepatocarcinogenesis induced by N-nitrosomorpholine in Sprague-Dawley rats. Tatsuta, M., Iishi, H., Baba, M. Int. J. Cancer (1989) [Pubmed]
  6. Induction of glucose-6-phosphate dehydrogenase by lipopolysaccharide contributes to preventing nitric oxide-mediated glutathione depletion in cultured rat astrocytes. García-Nogales, P., Almeida, A., Fernández, E., Medina, J.M., Bolaños, J.P. J. Neurochem. (1999) [Pubmed]
  7. Glucose-6-phosphate dehydrogenase is enriched in oligodendrocytes of the rat spinal cord. Enzyme histochemical and immunocytochemical studies. Kugler, P. Histochemistry (1994) [Pubmed]
  8. Hepatic hyperplasia and cancer in rats: metabolic alterations associated with cell growth. Rao, K.N., Elm, M.S., Kelly, R.H., Chandar, N., Brady, E.P., Rao, B., Shinozuka, H., Eagon, P.K. Gastroenterology (1997) [Pubmed]
  9. Preparation of a monoclonal antibody to rat liver glucose-6-phosphate dehydrogenase and the study of its immunoreactivity with native and inactivated enzyme. Dao, M.L., Johnson, B.C., Hartman, P.E. Proc. Natl. Acad. Sci. U.S.A. (1982) [Pubmed]
  10. Protection of a rat tracheal epithelial cell line from paraquat toxicity by inhibition of glucose-6-phosphate dehydrogenase. Lee, T.C., Lai, G.J., Kao, S.L., Ho, I.C., Wu, C.W. Biochem. Pharmacol. (1993) [Pubmed]
  11. Strain differences in the dose-response curves of adrenalectomized, starved-refed rats to dehydroepiandrosterone (DHEA). McIntosh, M.K., Berdanier, C.D. Proc. Soc. Exp. Biol. Med. (1988) [Pubmed]
  12. Metabolic effects of exercise. II. Residual metabolic effects of exercise in rats. Hebert, J.A., Lopez, A. Proc. Soc. Exp. Biol. Med. (1975) [Pubmed]
  13. Abnormalities in fracture healing induced by vitamin B6-deficiency in rats. Dodds, R.A., Catterall, A., Bitensky, L., Chayen, J. Bone (1986) [Pubmed]
  14. Peroxynitrite protects neurons against nitric oxide-mediated apoptosis. A key role for glucose-6-phosphate dehydrogenase activity in neuroprotection. García-Nogales, P., Almeida, A., Bolaños, J.P. J. Biol. Chem. (2003) [Pubmed]
  15. Arachidonic acid inhibits the insulin induction of glucose-6-phosphate dehydrogenase via p38 MAP kinase. Talukdar, I., Szeszel-Fedorowicz, W., Salati, L.M. J. Biol. Chem. (2005) [Pubmed]
  16. Glucose-6-phosphate dehydrogenase modulates cytosolic redox status and contractile phenotype in adult cardiomyocytes. Jain, M., Brenner, D.A., Cui, L., Lim, C.C., Wang, B., Pimentel, D.R., Koh, S., Sawyer, D.B., Leopold, J.A., Handy, D.E., Loscalzo, J., Apstein, C.S., Liao, R. Circ. Res. (2003) [Pubmed]
  17. Inhibition of the splicing of glucose-6-phosphate dehydrogenase precursor mRNA by polyunsaturated fatty acids. Tao, H., Szeszel-Fedorowicz, W., Amir-Ahmady, B., Gibson, M.A., Stabile, L.P., Salati, L.M. J. Biol. Chem. (2002) [Pubmed]
  18. Quantification of G6PD in small and large intestine of rat during aging. Biagiotti, E., Malatesta, M., Capellacci, S., Fattoretti, P., Gazzanelli, G., Ninfali, P. Acta Histochem. (2002) [Pubmed]
  19. Suppression of interleukin-1 beta-induced nitric oxide production in RINm5F cells by inhibition of glucose-6-phosphate dehydrogenase. Guo, L., Zhang, Z., Green, K., Stanton, R.C. Biochemistry (2002) [Pubmed]
  20. Changes in antioxidant lung protection after single intra-tracheal cadmium acetate instillation in rats. Salovsky, P., Shopova, V., Dancheva, V., Marev, R. Human & experimental toxicology. (1992) [Pubmed]
  21. Effects of sulfur dioxide inhalation on antioxidant enzyme activities in rat erythrocytes. Gümüşlü, S., Akbaş, H., Alicigüzel, Y., Ağar, A., Küçükatay, V., Yargiçoğlu, P. Industrial health. (1998) [Pubmed]
  22. Effects of diet and selected hormones on the activities of hepatic malic enzyme and glucose-6-phosphate dehydrogenase in infant, prematurely weaned rats. Back, D.W., Sohal, P.S., Angel, J.F. J. Nutr. (1985) [Pubmed]
  23. Purification of a new high activity form of glucose-6-phosphate dehydrogenase from rat liver and the effect of enzyme inactivation on its immunochemical reactivity. Dao, M.L., Watson, J.J., Delaney, R., Johnson, B.C. J. Biol. Chem. (1979) [Pubmed]
  24. Calvarial and limb bone cells in organ and monolayer culture do not show the same early responses to dynamic mechanical strain. Rawlinson, S.C., Mosley, J.R., Suswillo, R.F., Pitsillides, A.A., Lanyon, L.E. J. Bone Miner. Res. (1995) [Pubmed]
  25. Neural regulation of muscle glucose 6-phosphate dehydrogenase: effect of batrachotoxin and tetrodotoxin. Max, S.R., Deshpande, S.S., Albuquerque, E.X. J. Neurochem. (1982) [Pubmed]
  26. Ovarian dehydrogenase activities: suggested adrenal involvement in luteolysis. Castracane, V.D., Leathem, J.H. Proc. Soc. Exp. Biol. Med. (1976) [Pubmed]
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