The pentose phosphate pathway (also called Phosphogluconate Pathway, or Hexose Monophosphate Shunt [HMP shunt]) is a cytosolic process that serves to generate NADPH and the synthesis of pentose (5-carbon) sugars. There are two distinct phases in the pathway. The first is the oxidative phase, in which NADPH is generated, and the second is the non-oxidative synthesis of 5-carbon sugars. This pathway is an alternative to glycolysis. While it does involve oxidation of glucose, its primary role is anabolic rather than catabolic.

Uses

Located exclusively in the cytoplasm, the pathway is one of the three main ways the body creates molecules with reducing power, accounting for approximately 60% of NADPH production in humans.

One of the uses of NADPH in the cell is to prevent oxidative stress. It reduces the coenzyme glutathione, which converts reactive H₂O₂ into H₂O. If absent, the H₂O₂ would be converted to hydroxyl free radicals, which can attack the cell.

It is also used to generate hydrogen peroxide for phagocytes.^[1]

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

Regulation

Glucose-6-phosphate dehydrogenase is the rate-controlling enzyme of this pathway. It is allosterically stimulated by NADP⁺. The ratio of NADPH:NADP⁺ is normally about 100:1 in liver cytosol. This makes the cytosol a highly-reducing environment. Formation of NADP⁺ by a NADPH-utilizing pathway, thus, stimulates production of more NADPH.

See also

• G6PDH deficiency - A hereditary disease that disrupts the pentose phosphate pathway
• NADPH
• RNA

References

1. ^ Immunology at MCG 1/cytotox