pentose-phosphate pathway

The pentose phosphate pathway is primarily a cytoplasmic anabolic pathway that converts the 6 carbons of glucose to 5 carbon (pentose) sugars and reducing equivalents. (diagram) This pathway oxidizes glucose and its products can be completely oxidized to CO2 and water.

The pentose phosphate pathway regenerates NADPH from NADP+ through an oxidation/ reduction reaction that is coupled to the formation of ribose 5-phosphate from glucose 6-phosphate. The pentose phosphate pathway has both oxidative and non-oxidative arms.

Oxidation steps (diagram), utilizing glucose-6-phosphate (G6P) as the substrate, occur at the beginning of the pathway and generate NADPH. These reactions, catalyzed by glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase, generate one mole of NADPH each for every mole of glucose-6-phosphate (G6P) that enters the pentose phosphate pathway (PPP).

The non-oxidative reactions (diagram) of the pentose phosphate pathway primarily generate ribose 5-phosphate (R5P). The pentose phosphate pathway also converts dietary 5 carbon sugars into both 6 (fructose-6-phosphate) and 3 (glyceraldehyde-3-phosphate) carbon sugars which can then be utilized by the pathways of glycolysis. The primary enzymes involved in the non-oxidative steps of the PPP are transaldolase and transketolase.

In summary, the pentose phosphate pathway primarily generates NADPH, ribose 5-phosphate, fructose 6-phosphate, and glyceraldehyde 3-phosphate (diagram, diagram). Glyceraldehyde-3-phosphate can be shunted to glycolysis and oxidized to pyruvate. Alternatively, glyceraldehyde-3-phosphate can be utilized by the gluconeogenic enzymes to generate more 6 carbon sugars (fructose-6-phosphate or glucose-6-phosphate).

NADPH is employed in reductive reactions in anabolism, particularly in the synthesis of fatty acids. In red blood cells (erythrocytes), the major role of NADPH is to reduce the disulfide form of glutathione to the sulfhydryl form. Reduced glutathione is important for maintenance of the normal structure of eythrocytes and for maintaining hemoglobin in the ferrous state [Fe(II)]. Deficiency of the oxidative pathway enzyme glucose-6-phosphate dehydrogenase causes hematologic problems because the inability to maintain reduced glutathione results in accumulation of damaging peroxides (H2O2). G6PD-deficiency is associated, however, with resistance to the malarial parasite Plasmodium falciparum because the weakened RBC membrane (erythrocytic host cell) cannot sustain the parasitic life cycle long enough for productive growth.