What has passed is prolog: new cellular and physiological roles of G6PD.
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.
a Department of Medical Biotechnology and Laboratory Sciences , College of Medicine, Chang Gung University , Taoyuan , Taiwan.|b Healthy Aging Research Center, Chang Gung University , Taoyuan , Taiwan.
Hung-Chi
HC
Yang
a Department of Medical Biotechnology and Laboratory Sciences , College of Medicine, Chang Gung University , Taoyuan , Taiwan.
Yi-Hsuan
YH
Wu
a Department of Medical Biotechnology and Laboratory Sciences , College of Medicine, Chang Gung University , Taoyuan , Taiwan.
Hui-Ya
HY
Liu
c Department of Biochemistry and Molecular Pharmacology , New York University School of Medicine , New York , NY , USA.
Arnold
A
Stern
a Department of Medical Biotechnology and Laboratory Sciences , College of Medicine, Chang Gung University , Taoyuan , Taiwan.|b Healthy Aging Research Center, Chang Gung University , Taoyuan , Taiwan.|d Department of Pediatric Hematology/Oncology , Chang Gung Memorial Hospital , Linkou , Taiwan.
Daniel Tsun-Yee
DT
Chiu
D000818:Animals; D005955:Glucosephosphate Dehydrogenase Deficiency; D006801:Humans; D051379:Mice; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species
D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species
G6PD; NADPH; NOS; NOX; oxidative stress; reactive oxygen and nitrogen species