6-phosphogluconate dehydrogenase, decarboxylating (6PGD)

6-phosphogluconate dehydrogenase, decarboxylating (6PGD) is a vital enzyme in the oxidative branch of the pentose phosphate pathway, where it catalyzes the conversion of 6-phosphogluconate into ribulose 5-phosphate and generates NADPH (Wikipedia, 2024). This process is essential for maintaining cellular redox balance and providing the building blocks for nucleotide and lipid biosynthesis, making it particularly important for rapidly dividing cells (NIH, 2026). In various malignancies, including lung, breast, and leukemia, 6PGD is frequently overexpressed and serves as a metabolic driver of tumor progression and chemoresistance (Ovid, 2022). Beyond its role in cancer, 6PGD is a promising therapeutic target for treating parasitic infections like malaria and African trypanosomiasis, as these organisms rely heavily on the enzyme for antioxidant defense (Wikipedia, 2024; NIH, 2023). Small molecule inhibitors such as physcion have demonstrated the ability to suppress tumor growth by inducing oxidative stress and activating the AMPK signaling pathway (NIH, 2016). However, a significant therapeutic challenge is the potential for hemolytic anemia, as red blood cells are highly sensitive to disruptions in NADPH production (NIH, 2016). Consequently, drug development efforts focus on achieving high selectivity for the target in diseased cells or parasites while sparing healthy human tissues (IUCr, 2021).

Other names

6-phosphogluconate dehydrogenasePhosphogluconate dehydrogenase6-phospho-D-gluconate dehydrogenasePGD6PGDHGND

Inhibition of 6-phosphogluconate dehydrogenase activity, leading to depletion of NADPH and ribulose 5-phosphate, induction of oxidative stress, and activation of the AMPK pathway.