Validating the assessment of glucose 6 phosphate dehydrogenase g6pd

21 Aug

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked enzymopathy that affects hundreds of millions of people worldwide, conferring increased risk of neonatal jaundice and oxidant-induced hemolytic anemia.Screening and diagnosis of G6PD deficiency is currently performed using genetic or biochemical assays, the former being cost ineffective in populations with significant allelic heterogeneity, and the latter being limited in ability to detect female heterozygotes.Glucose-6-phosphate dehydrogenase (G6PD) is a housekeeping enzyme that catalyses the rate-limiting first step in the pentose phosphate pathway, where it produces nicotinamide adenine dinucleotide phosphate (NADPH), a critical cofactor in a variety of metabolic processes.In the red blood cell (RBC), G6PD activity is especially important as the principal source of reducing power to regenerate the antioxidant glutathione.The immediate impact of this model will be in advancing the development antimalarial drugs.

G6PD converts glucose-6-phosphate to 6-phosphoglyconolactone in the first step of the pentose phosphate pathway (PPP), this reaction also produces nicotinamide adenine dinucleotide phosphate-oxidase (NADPH) from nicotinamide adenine dinucleotide phosphate (NADP).Individuals with G6PD-deficient RBCs are thus at risk for hemolysis precipitated by oxidants found in certain foods or chemotherapeutics, or generated during severe infections.One especially important example of drug-induced hemolysis is that caused by primaquine, one of few antimalarial drugs active against both Plasmodium vivax hypnozoites and P. As areas of high malaria transmission overlap geographically with areas of high G6PD deficiency prevalence, this drug sensitivity reaction is an important public health concern, especially given recent interest in reducing and eliminating malaria transmission.Treatment of SCID mice engrafted with G6PD-deficient hu RBCs with primaquine, an 8-AQ, resulted in a dose-dependent selective loss of hu RBCs.To validate the specificity of this model, we tested known nonhemolytic antimalarial drugs: mefloquine, chloroquine, doxycycline, and pyrimethamine.