In intermediary metabolism G6PD is aptly depicted as the first step in the pentose phosphate pathway. However, several lines of evidence indicate that its most essential role is not to produce pentose, but rather to produce reductive potential in the form of NADPH. Recently, G6PD-null mouse embryos have been obtained by targeted inactivation of G6PD in embryonic stem cells. From a detailed analysis of hemizygous mutant embryos, which die by day 10.5, it was inferred that the cause of death is precisely the onset of aerobic metabolism. Interestingly, heterozygous embryos also die, somewhat later, only if their G6PD-null gene is of maternal origin: in this case the cause of death is a defective placenta, as a consequence of the selective inactivation of the paternal X chromosome in extra-embryonic tissues.
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