Pentose phosphate pathway

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The pentose phosphate pathway's Nonoxidative phase
The pentose phosphate pathway's Nonoxidative phase

The pentose phosphate pathway (also called Phosphogluconate Pathway, or Hexose Monophosphate Shunt [HMP 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 molecules with reducing power, accounting for approximately 10% 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.

Contents

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

The overall reaction for this process is:
Glucose 6-phosphate + 2 NADP+ + H2O → ribulose 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 6-phosphoglucolactonase.

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


Oxidative phase of pentose phosphate pathway
Oxidative phase of pentose phosphate pathway

  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 (transketolase)


For a thorough scientific overview of ribose-5-phosphate isomerase deficiency and transaldolase deficiency, one can consult the supplement of chapter 73 in OMMBID.[1] For more online resources and references, see inborn error of metabolism.




  1. ^ Charles Scriver, Beaudet, A.L., Valle, D., Sly, W.S., Vogelstein, B., Childs, B., Kinzler, K.W. (2006). The Online Metabolic and Molecular Bases of Inherited Disease. New York: McGraw-Hill. - Free summaries of 255 chapters, full text through many universities and organizations. There is also the OMMBID blog.


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