Glucose‐6‐phosphate dehydrogenase: a “housekeeping” enzyme subject to tissue‐specific regulation by hormones, nutrients, and oxidant stress

Abstract

The enzyme, glucose-6-phosphate dehydrogenase (G6PDH, EC1.1.1.49), has long been considered and studied as the archetypical X-linked "housekeeping" enzyme that is present in all cells, where it plays the key role in regulating carbon flow through the pentose phosphate pathway. Specifically, the enzyme catalyzes the first reaction in the pathway leading to the production of pentose phosphates and reducing power in the form of NADPH for reductive biosynthesis and maintenance of the redox state of the cell. It was in this latter function that the crucial importance of the enzyme was first appreciated with the description of the human deficiency syndrome. While the gene can be considered to be a constitutively expressed "housekeeping" gene in many tissues, there are several other tissues (liver, adipose, lung, and proliferating cells) wherein modulation of cellular G6PDH activity represents an important component of the integrated response to external stimuli (hormones, growth factors, nutrients, and oxidant stress). In this regard, adaptive regulation of G6PDH has been found to be exerted at transcriptional and posttranscriptional levels. However, the regulation observed is tissue-specific, which elicits the central question of this review, "How can the G6PDH gene be constitutively expressed in some tissues while displaying adaptive regulation in others when there exists a single transcription unit for the gene?" Future studies utilizing cloned genomic fragments of the human and other mammalian G6PDH genes should provide answers to this question.

Lipotropes promote immunobiochemical plasticity and protect fish against low-dose pesticide-induced oxidative stress

“…Glucose-6-phosphate dehydrogenase (D-glucose-6-phosphate: NADP+oxidoreductase EC 1.1.1.49; G6PD) catalyzes the first and rate-limiting step of the pentose phosphate pathway, an important source of cellular reduced nicotinamide adenine dinucleotide phosphate (NADPH) which is essential for many types of biosyntheses as well as DNA/RNA synthesis and three to seven carbon sugars or sugar phosphates for many other uses (Carvalho et al 1993;Kletzien et al 1994). NADPH is used to generate the reduced glutathione and thioredoxin that are primary sources of reducing power for antioxidant reactions.…”

Effects of continuous hypoxia on energy metabolism in cultured cerebro-cortical neurons

“…The product of HK (glucose-6-phosphate) is also a substrate for glucose-6-phosphate dehydrogenase, the first enzyme of the pentose phosphate pathway. NADPH production in the pentose phosphate pathway (Kletzien et al, 1994;Almeida et al, 2002) contributes to the regulation of reduced glutathione (GSH), an important antioxidant; thus, tight homeostatic regulation of this pathway (both flux and intermediates/products) in the presence of large glycolytic fluxes could be beneficial. Concentrations of GSH and GSSG in 'mature' primary neurons are not affected by hypoxia, unlike combined glucose and oxygen deprivation, which increases GSSH at the expense of GSH (Almeida et al, 2002).…”

Diallyl sulfide protects against N -nitrosodiethylamineinduced liver tumorigenesis: Role of aldose reductase

“…G6PD is a housekeeping enzyme that produces riboses, which are incorporated into nucleotides and nucleic acids, and NADPH, the major cytoplasmic reducing compound [38] . NADPH is necessary for reduction of oxidized glutathione by glutathione reductase [39] , and is a substrate for phase Ⅰ and Ⅱ biotransformation and detoxification enzymes [36] .…”