FIG. 4.

Antioxidant enzyme deficiency and oxidative enzymopathies. The antioxidant enzymes glutathione peroxidase-1 and -3 (GPx) and glucose-6-phosphate dehydrogenase (G6PD) limit intracellular oxidant stress through a series of coupled reactions that (re)generate reduced glutathione (GSH). GPx activity may be decreased by a heritable deficiency of the enzyme or acquired, as occurs with hyperhomocysteinemia. Similarly, G6PD activity may be decreased by a heritable deficiency of the enzyme or acquired, as occurs in the hyperaldosteronism or hyperglycemia associated with diabetes mellitus. The net result of deficient activity of either of these antioxidant enzymes is an increase in ROS and a decrease in bioavailable NO^•. This pathobiologic state results in endothelial dysfunction and impaired vascular reactivity, and, in the case of glutathione peroxidase-3 deficiency, platelet activation and arterial thrombosis. H₂O₂, hydrogen peroxide; GSSG, oxidized glutathione; GSSG reductase, glutathione reductase; G-6-P, glucose-6-phosphate; 6-PG, 6-phosphogluconate. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article at www.liebertonline.com/ars).