G6pdx, also known as glucose-6-phosphate 1-dehydrogenase X, is involved in the pentose phosphate pathway. It catalyzes the rate-determining step in this pathway, producing NADPH which is crucial for glutathione recycling, an important antioxidant defense mechanism [1]. This pathway and G6pdx's role are of great biological importance as they help cells cope with oxidative stress. Genetic models, such as knockout mouse models, are valuable for studying G6pdx.

In G6PD-deficient (G6PDX) mice, which serve as a model for human G6PD deficiency, there are various impacts on physiological processes. Myocardial infarction or pressure-overload induced heart failure led to more severe left ventricular dilation and dysfunction in G6PDX mice compared to wild-type mice, indicating that G6PD deficiency may increase the risk of heart failure development. This suggests that G6PD deficiency increases myocardial oxidative stress and subsequent damage, as shown by increased lipid peroxidation products and decreased aconitase activity [3]. After myocardial infarction in mice, changes in glucose metabolism and the pentose phosphate pathway, including increased expression of G6pdx, were associated with macrophage polarization. This indicates that G6pdx may play a role in the metabolic reprogramming underlying macrophage polarization after myocardial infarction [2].

In conclusion, G6pdx is essential for the pentose phosphate pathway and antioxidant defense. Studies using G6PD-deficient mouse models have revealed its significance in cardiovascular disease, especially in relation to heart failure and myocardial infarction. These models also suggest a role for G6pdx in macrophage polarization processes following myocardial infarction, contributing to our understanding of how G6pdx-related metabolic changes impact specific biological processes and disease conditions.