2014
DOI: 10.1002/embj.201387224
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Regulation of G6PD acetylation by KAT9/SIRT2 modulates NADPH homeostasis and cell survival during oxidative stress

Abstract: Glucose-6-phosphate dehydrogenase (G6PD) is a key enzyme in the pentose phosphate pathway (PPP) and plays an essential role in the oxidative stress response by producing NADPH, the main intracellular reductant. G6PD deficiency is the most common human enzyme defect, affecting more than 400 million people worldwide. Here, we show that G6PD is negatively regulated by acetylation on lysine 403 (K403), an evolutionarily conserved residue. The K403 acetylated G6PD is incapable of forming active dimers and displays … Show more

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Cited by 204 publications
(267 citation statements)
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“…This cell line has a glucose 6-phosphate dehydrogenase (G6PD) A phenotype, meaning it lacks the proper functioning of this enzyme in the pentose phosphate pathway. 13 G6PD is the rate-limiting enzyme in this pathway; its deficiency blocks the conversion of glucose-6-phosphate to 6-phosphoglucono-D-lactone and in the process prevents the conversion of NADPH to NADP + , a required step in GSH synthesis. 14 This suggests that a GSH deficiency may play an important role in potentiating the activity, something previously demonstrated when A2780 cells were co-incubated with low levels of the GSH inhibitor, L-buthionine sulfoximine.…”
Section: Antiproliferative Activitymentioning
confidence: 99%
“…This cell line has a glucose 6-phosphate dehydrogenase (G6PD) A phenotype, meaning it lacks the proper functioning of this enzyme in the pentose phosphate pathway. 13 G6PD is the rate-limiting enzyme in this pathway; its deficiency blocks the conversion of glucose-6-phosphate to 6-phosphoglucono-D-lactone and in the process prevents the conversion of NADPH to NADP + , a required step in GSH synthesis. 14 This suggests that a GSH deficiency may play an important role in potentiating the activity, something previously demonstrated when A2780 cells were co-incubated with low levels of the GSH inhibitor, L-buthionine sulfoximine.…”
Section: Antiproliferative Activitymentioning
confidence: 99%
“…Abnormalities in its levels may have pathological implications. It also plays vital roles in managing oxidative stress within cells [38] . This suggests that caffeine mechanism might stimulate basal glucose metabolism more, and this is logical as it is widely acclaimed to enhance performance especially at moderate doses.…”
Section: Effects Of Caffeine and Cannabis On Enzymesmentioning
confidence: 99%
“…G6PD is the first enzyme of the PPP and it catalyzes the oxidation of glucose-6-phosphate to 6-phosphogluconolactone [Zhao et al, 2014]. This enzyme is a key modulator of the metabolic rate in the PPP, a route that provides the organism with NADPH, which is involved in several biological processes, but mainly as a reducing equivalent donor for fatty acid synthesis and ri-bose-5-phosphate for nucleotide synthesis [Wang et al, 2014b]. G6PD activity has a fundamental role in counteracting oxidative stress by maintaining a reduced environment for the proper functioning of the cell.…”
Section: Discussionmentioning
confidence: 99%