Pentose phosphate pathway

The penthose phosphate pathway (also known as the Hexose Monophosphate Shunt) is a 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. The pathway is one of the three main ways the body creates reducing molecules to prevent oxidative stress, accounting for approximately 10% of NADPH production in humans.

Oxidative phase

In this phase, two molecules of NADPH⁺ are reduced to NADPH, utilising the energy from the conversion of glucose 6-phosphate into ribose 5-phosphate.

The overall reaction for this process is:
Glucose 6-phosphate + 2 NADPH⁺ + H₂O → ribose 5-phosphate + 2 NADPH ⁺ 2 H⁺ + CO₂

The first step in this series of reactions is the dehydrogenation of glucose 6-phosphate into 6-phosphoglucono-δ-lactone. This reaction is catalyzed by glucose 6-phosphate dehydrogenase. The hydroxyl group located on carbon 1 of glucose 6-phosphate is converted into a keto group, and in the process, NADPH is generated.

The second step is the hydrolysis of 6-phosphoglucono-δ-lactone to 6-phosphogluconate, which is catalyzed by a lactonase.

The third step is the oxidative decarboxylation of 6-phosphogluconate to ribulose 5-phosphate. This reaction is catalyzed by 6-phosphogluconate dehydrogenase and NADP⁺ is the electron acceptor, generating another molecule of NADPH.

The final step is the isomerization (catalyzed by phosphopentose isomerase) of ribulose 5-phosphate into ribose 5-phosphate.

The entire set of reactions can be summarized as follows:

1. Glucose 6-phosphate + NADP+ → 6-phosphoglucono-δ-lactone + NADPH
2. 6-phosphoglucono-δ-lactone + H₂O → 6-phosphogluconate + H⁺
3. 6-phosphogluconate + NADP⁺ → ribulose 5-phosphate + NADPH + CO₂

Synthesis of sugar

Non-oxidative phase

1. ribulose 5-phosphate → ribose 5-phosphate (phosphopentose isomerase)
2. ribulose 5-phosphate → xylulose 5-phosphate (phosphopentose epimerase)
3. xylulose 5-phosphate + ribose 5-phosphate → glyceraldehyde 3-phosphate + Sedoheptulose 7-phosphate (transketolase)
4. sedoheptulose 7-phosphate + glyceraldehyde 3-phosphate → erythrose 4-phosphate + fructose 6-phosphate (transaldolase)
5. xylulose 5-phosphate + erythrose 4-phosphate → glyceraldehyde 3-phosphate + fructose 6-phosphate (transaldolase)

See also

• G6PDH deficiency – A hereditary disease which disrupts the pentose phosphate pathway.
• NADPH
• RNA