The global role of G6PD in infection and immunity.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzymopathy in humans. G6PD is an essential enzyme in the pentose phosphate pathway (PPP), generating NADPH needed for cellular biosynthesis and reactive oxygen species (ROS) homeostasis, the latter especially key in red blood cells (RBCs). Beyond the RBC, there is emerging evidence that G6PD exerts an immunologic role by virtue of its functions in leukocyte oxidative metabolism and anabolic synthesis necessary for immune effector function. We review these here, and consider the global immunometabolic role of G6PD activity and G6PD deficiency in modulating inflammation and immunopathology.

G6PD deficiency mediated impairment of iNOS and lysosomal acidification affecting phagocytotic clearance in microglia in response to SARS-CoV-2.

The glucose-6-phosphate dehydrogenase (G6PD) deficiency is X-linked and is the most common enzymatic deficiency disorder globally. It is a crucial enzyme for the pentose phosphate pathway and produces NADPH, which plays a vital role in regulating the oxidative stress of many cell types. The deficiency of G6PD primarily causes hemolytic anemia under oxidative stress triggered by food, drugs, or infection. G6PD-deficient patients infected with SARS-CoV-2 showed an increase in hemolysis and thrombosis. Patients also exhibited prolonged COVID-19 symptoms, ventilation support, neurological impacts, and high mortality. However, the mechanism of COVID-19 severity in G6PD deficient patients and its neurological manifestation is still ambiguous. Here, using a CRISPR-edited G6PD deficient human microglia cell culture model, we observed a significant reduction in NADPH level and an increase in basal reactive oxygen species (ROS) in microglia. Interestingly, the deficiency of the G6PD-NAPDH axis impairs induced nitric oxide synthase (iNOS) mediated nitric oxide (NO) production, which plays a fundamental role in inhibiting viral replication. Surprisingly, we also observed that the deficiency of the G6PD-NADPH axis reduced lysosomal acidification and free radical production, further abrogating the lysosomal clearance of viral particles. Thus, impairment of NO production, lysosomal functions, and redox dysregulation in G6PD deficient microglia altered innate immune response, promoting the severity of SARS-CoV-2 pathogenesis.

Glicose-6-fosfato desidrogenase: aspectos clínicos / Glucose-6-phosphate dehydrogenases: clinical aspects

In this article, the authors presente a review about the behaviour of G6PD in relation to pathologies other than hemolytic anemias, which are the many diagnostic use of the enzyme

Estudo da dinâmica insulínica e da secreçäo de cortisol em pacientes com deficiência de glicose-6-fosfato desidrogenase / Insulin dinamic and cortisol secretion study in patients with glicose-6-phosphate dehydrogenase deficiency

Na presente pesquisa, o objetivo foi avaliar de forma mais precisa a secreçäo da insulina através da quantificaçäo do peptideo C plasmático após estímulo glicídico, assim como, após a L-arginina, outro estimulante da secreçäo de insulina, além da sensibilidade periférica à insulina. Constou dos objetivos avaliar a secreçäo de cortisol após estímulo com ACTH. Para tanto, foram estudados 11 indivíduos com deficiência de G-6-PD e 11 indivíduos controle que formaram o grupo I e foram submetidos aos testes para avaliar a funçäo secretória da célula pancreática (teste endovenoso de tolerância à glicose - TETG e teste de arginina) e a sensibilidade periférica à insulina (teste de tolerância à insulina - TTI). E, o grupo II composto com 12 indivíduos com deficiência de G-6-PD e 16 indivíduos com deficiência de G-6-PD e 16 indivíduos controle que foram submetidos à estimulaçäo das adrenais com ACTH (Teste de cortisol). Para os dois grupos de estudo os procedimentos experimentais foram realizados após jejum de 12-14 h. Os resultados demonstram que pacientes com deficiência de G-6-PD apresentam diminuiçäo na secreçäo de insulina (fase rápida) após estímulo com glicose e L-arginina, sensibilidade periférica à insulina semelhante a de indivíduos controle e secreçäo de cortisol diminuida durante a primeira hora após estimulaçäo com ACTH