6Phosphogluconate

6-Phosphogluconate, often abbreviated as 6PG, is a phosphorylated sugar acid that functions as an intermediate in the oxidative phase of the pentose phosphate pathway (PPP). It is produced from glucose-6-phosphate when glucose-6-phosphate dehydrogenase oxidizes the substrate and reduces NADP+ to NADPH, initially forming 6-phosphoglucono-δ-lactone, which is then hydrolyzed to 6-phosphogluconate. This sequence links glucose metabolism to reductive biosynthesis and nucleotide precursor production.

In the next PPP step, 6-phosphogluconate is acted upon by 6-phosphogluconate dehydrogenase, which oxidatively decarboxylates it to ribulose-5-phosphate, generating a second molecule of NADPH and releasing CO2. The ribulose-5-phosphate can be isomerized to ribose-5-phosphate for nucleotide synthesis or rearranged into xylulose-5-phosphate for the non-oxidative branch of the pathway, enabling interconversion of various sugar phosphates as needed by the cell. In some bacteria, 6-phosphogluconate can also enter the Entner-Doudoroff pathway, where it is dehydrated to 2-keto-3-deoxy-6-phosphogluconate (KDPG) and subsequently cleaved to glyceraldehyde-3-phosphate and pyruvate.

Biologically, 6-phosphogluconate is a key stepping stone in cellular NADPH production, which supports fatty acid synthesis, cholesterol synthesis, and detoxification processes. Its formation and turnover help balance the cell’s anabolic needs with its redox state, while also connecting with ribose synthesis for nucleotide production. It is commonly found in the cytosol of organisms that utilize the PPP.