pathway to use in the reduction of glutathione. Hydrogen peroxide is also generated for phagocytes in a process often referred to as a respiratory burst. Phases Oxidative phase In this phase, two molecules of NADP+ are reduced to NADPH, utilizing the energy from the conversion of glucose-6-phosphate into ribulose 5-phosphate. The entire set of reactions can be summarized as follows: The overall reaction for this process is: Glucose 6-phosphate + 2 NADP+ + H2O → ribulose 5-phosphate + 2 NADPH + 2 H+ + CO2 Non-oxidative phase Net reaction: 3 ribulose-5-phosphate → 1 ribose-5-phosphate + 2 xylulose-5-phosphate → 2 fructose-6-phosphate + glyceraldehyde-3-phosphate Regulation Glucose-6-phosphate dehydrogenase is the rate-controlling enzyme of this pathway. It is allosterically stimulated by NADP+ and strongly inhibited by NADPH. The ratio of NADPH:NADP+ is the primary mode of regulation for the enzyme and is normally about 100:1 in liver cytosol. This makes the cytosol a highly-reducing environment. An NADPH-utilizing pathway forms NADP+, which stimulates Glucose-6-phosphate dehydrogenase to produce more NADPH. This step is also inhibited by acetyl CoA. G6PD activity is also post-translationally regulated by cytoplasmic deacetylase SIRT2. SIRT2-mediated deacetylation and activation of G6PD stimulates oxidative branch of PPP to supply cytosolic NADPH to counteract oxidative damage or support de novo lipogenesis. Erythrocytes Several deficiencies in the level of activity (not function) of glucose-6-phosphate dehydrogenase have been observed to be associated with resistance to the malarial parasite Plasmodium falciparum among individuals of Mediterranean and African descent. The basis for this resistance may be a weakening of the red cell membrane (the erythrocyte is the host cell for the parasite) such that it cannot sustain the parasitic life cycle long enough for productive growth. See also G6PD deficiency – A hereditary disease that disrupts the pentose phosphate pathway RNA Thiamine deficiency Frank Dickens FRS References External links The chemical logic behind the pentose phosphate pathway Pentose phosphate pathway Map – Homo sapiens Metabolic pathways Phosphorus