6PGL

6-Phosphogluconolactonase (6PGL) is an enzyme of the pentose phosphate pathway. It catalyzes the hydrolysis of 6-phosphoglucono-δ-lactone to 6-phosphogluconate, the second step of the oxidative branch after glucose-6-phosphate dehydrogenase.

The reaction performed by 6PGL prepares the lactone for subsequent oxidation by 6-phosphogluconate dehydrogenase, enabling continued flux through the pathway. This pathway supports the production of NADPH, which is used in reductive biosynthesis and antioxidant defense, and provides ribose-5-phosphate for nucleotide synthesis.

6PGL is found in a wide range of organisms, including bacteria, archaea, and eukaryotes. In humans, the enzyme is encoded by the PGLS gene and is predicted to function in the cytosol. Its activity is integrated with other steps of the pentose phosphate pathway to maintain cellular redox balance and supply metabolic intermediates.

Biochemically, 6PGL is a relatively small, soluble protein that may exist as a monomer or in oligomeric forms depending on the species. The active site contains conserved residues that promote hydrolysis of the lactone ring to yield 6-phosphogluconate, enabling the continuation of the oxidative branch of the pathway.

Because 6PGL lies between glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase, it contributes to PPP flux and influences cellular metabolism, redox status, and anabolic precursor availability.