highlight all areas / label key areas
The Pentose Phosphate pathway is a pathway of glucose metabolism that occurs in parallel to Glycolysis. It diverts from glycolysis at glucose-6-phosphate (see Glycolysis pathway). Although it involves the oxidation of glucose, it functions primarily to provide building blocks for anabolic pathways.
The Pentose Phosphate pathway consists of a proximal oxidative phase and a distal non-oxidative phase. In the oxidative phase, NADPH is generated and is used for reductive biosynthetic reactions such as the synthesis of fatty acids (see Fatty Acid Synthesis pathway). NADPH can also prevent oxidative stress by reactive oxygen species (ROS) by reducing glutathione, which buffers ROS.
The non-oxidative phase produces ribose-5-phosphate, which can be used for nucleotide synthesis. The non-oxidative phase of the pathway also produces fructose-6-phosphate, a glycolytic intermediate that can re-enter glycolysis (see Glycolysis pathway) or under conditions of high reductive demand, can re-synthesise glucose-6-phosphate for re-entry into the Pentose Phosphate pathway to continue generation of NADPH. Flux through this pathway is increased in many cancers to support the rapid growth of cancer cells.
Key points:
Ribose-5-phosphate (R5P) is produced by the last step of the oxidative phase of the Pentose Phosphate pathway. R5P is important for the generation of nucleotides, which are required for DNA and RNA synthesis. R5P is a precursor to both purine and pyrimidine nucleotides.
Glucose-6-phosphate dehydrogenase (G6PDH) is the rate limiting enzyme controlling flux through the Pentose Phosphate pathway. It catalyses the conversion of glucose-6-phosphate to 6-phospho-glucono-1,5-lactone:
Glucose-6-phosphate + NADP+ → 6-phospho-glucono-1,5-lactone + NADPH + H+
The NADPH produced by this reaction provides reducing equivalents for the synthesis of fatty acids (see Fatty Acid Synthesis pathway) and for reduction of glutathione.
G6PDH is allosterically activated by NADP+, and its activity is also increased transcriptionally and by post-translational modifications in response to insulin and other growth factor signalling.