What has passed is prolog: new cellular and physiological roles of G6PD

Hung Chi Yang, Yi Hsuan Wu, Hui Ya Liu, Arnold Stern, Daniel Tsun Yee Chiu*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

48 Scopus citations

Abstract

G6PD deficiency has been the most pervasive inherited disorder in the world since having been discovered. G6PD has an antioxidant role by functioning as a major nicotinamide adenine dinucleotide phosphate (NADPH) provider to reduce excessive oxidative stress. NADPH can produce reactive oxygen species (ROS) and reactive nitrogen species (RNS) mediated by NADPH oxidase (NOX) and nitric oxide synthase (NOS), respectively. Hence, G6PD also has a pro-oxidant role. Research in the past has focused on the enhanced susceptibility of G6PD-deficient cells or individuals to oxidative challenge. The cytoregulatory role of G6PD has largely been overlooked. By using a metabolomic approach, it is noted that upon oxidant challenge, G6PD-deficient cells will reprogram the GSH metabolism from regeneration to synthesis with exhaustive energy consumption. Recently, new cellular/physiologic roles of G6PD have been discovered. By using a proteomic approach, it has been found that G6PD plays a regulatory role in xenobiotic metabolism possibly via NOX and the redox-sensitive Nrf2-signaling pathway to modulate the expression of xenobiotic-metabolizing enzymes. Since G6PD is a key regulator responsible for intracellular redox homeostasis, G6PD deficiency can alter redox balance leading to many abnormal cellular effects such as the cellular inflammatory and immune response against viral infection. G6PD may play an important role in embryogenesis as G6PD-knockdown mouse cannot produce offspring and G6PD-deficient C. elegans with defective egg production and hatching. This array of findings indicates that the cellular and physiologic roles of G6PD, other than the classical role as an antioxidant enzyme, deserve further attention.

Original languageEnglish
Pages (from-to)1047-1064
Number of pages18
JournalFree Radical Research
Volume50
Issue number10
DOIs
StatePublished - 02 10 2016

Bibliographical note

Publisher Copyright:
© 2016 Informa UK Limited, trading as Taylor & Francis Group.

Keywords

  • G6PD
  • NADPH
  • NOS
  • NOX
  • oxidative stress
  • reactive oxygen and nitrogen species

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