Pentose Phosphate Pathway

The pentose phosphate pathway (also called the phosphogluconate pathway and the hexose monophosphate shunt ) is a metabolic pathway parallel to glycolysis . [1] It generates NADPH and pentose (5 – carbon sugar ) as well as ribose 5-phosphate , a precursor for the synthesis of nucleotides . [2] While the pentose phosphate pathway involves the oxidation of glucose , its primary role is anabolism rather than catabolism., The pathway is particularly important in red blood cells (erythrocytes).

Pentose Phosphate Pathway

There are two distinct phases in the route. The first is the oxidative step, in which NADPH is generated, and the second is the non-oxidative synthesis of 5-carbon sugars . For most organisms, the pentose phosphate pathway occurs in the cytosol ; Most of the stages in plants occur in plastids . [3]

Like glycolysis , the pentose phosphate pathway appears to have a very ancient evolutionary origin. The reactions of this pathway are mostly enzyme-catalyzed in modern cells, however, they also occur non-enzymatically under conditions that mimic the Archean Ocean, and metal ions , especially iron ions (Fe(II)) ) is inspired by. [4] This suggests that the pathway may have originated from the prebiotic world.


The primary outcomes of the route are:

  • The generation of reducing counterparts, in the form of NADPH, is used in reductive biosynthesis reactions (such as fatty acid synthesis ) within cells.
  • Production of ribose 5-phosphate (R5P), which is used in the synthesis of nucleotides and nucleic acids.
  • Production of erythrose 4-phosphate (E4P) used in the synthesis of aromatic amino acids

Aromatic amino acids, in turn, are precursors of several biosynthetic pathways, including lignin , in wood.
Dietary pentose sugars derived from the digestion of nucleic acids can be metabolized through the pentose phosphate pathway, and the carbon skeleton of dietary carbohydrates can be converted into glycolytic/gluconeogenic intermediates.

In mammals, PPP occurs exclusively in the cytoplasm. In humans, it is found most active in the liver, mammary glands and adrenal cortex. PPP is one of three main ways the body creates molecules with reducing power, which are responsible for approximately 60% of NADPH production in humans.

One of the uses of NADPH in the cell is to prevent oxidative stress . It reduces glutathione via glutathione reductase , which converts reactive H2O2 into H2O by glutathione peroxide . If absent, H2O2 will be converted by Fenton chemistry into hydroxyl free radicals, which can attack the cell. Erythrocytes, for example, generate large amounts of NADPH through the pentose phosphate pathway to be utilized in glutathione deficiency.

Hydrogen peroxide is also generated for phagocytes in a process often referred to as a respiratory burst . [5]

steps of

oxidative phase

Pentose Phosphate Pathway
Pentose Phosphate Pathway

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

Oxidative step of the pentose phosphate pathway.
Glucose-6-phosphate ( 1 ), 6-phosphoglucono-a-lactone ( 2 ), 6- phosphogluconate ( 3 ), ribulose 5-phosphate ( 4 )

The whole set of reactions can be summarized as:

Glucose 6-Phosphate + NADP+→ 6-phosphoglucono-δ-lactone + NADPHGlucose 6-phosphate dehydrogenaseDehydration. Glucose is converted to the hydroxyl carbonyl at carbon 1 of the 6-phosphate, generating a lactone, and in the process, generating NADPH.
6-Phosphoglucono-δ-Lactone + H 2 O→ 6-phosphogluconate + H +6-phosphogluconolactoneasehydrolysis
6-Phosphogluconate + NADP +→ Ribulose 5-phosphate + NADPH + CO 26-phosphogluconate dehydrogenaseOxidative decarboxylation. NADP + is the electron acceptor, generating another molecule of NADPH, a CO2 , and ribulose 5-phosphate.

The overall response to this process is:Glucose 6-phosphate + 2 NADP + + H 2 O → Ribulose 5-phosphate + 2 NADPH + 2 H + + CO 2

non-oxidative phase

Non-oxidative step of the pentose phosphate pathway

Ribulose 5-phosphate→ Ribose 5-phosphateRibose-5-phosphate isomerase
Ribulose 5-phosphate→ Xylulose 5-phosphateRibulose 5-phosphate 3-epimerase
Xylulose 5-Phosphate + Ribose 5-Phosphate→ Glyceraldehyde 3-phosphate + Cedoheptulose 7-phosphatetransketolase
Cedoheptulose 7-Phosphate + Glyceraldehyde 3-Phosphate→ Erythrose 4-phosphate + Fructose 6-phosphatetransaldolase
Xylulose 5-Phosphate + Erythrose 4-Phosphate→ Glyceraldehyde 3-phosphate + Fructose 6-phosphatetransketolase

Pure reaction: 3 ribulose-5-phosphate → 1 ribose-5-phosphate + 2 xylulose-5-phosphate → 2 fructose-6-phosphate + glyceraldehyde-3-phosphate


Glucose-6-phosphate dehydrogenase is the rate controlling enzyme of this pathway. It is fully stimulated by NADP + and strongly inhibited by NADPH. [6] The ratio of NADPH:NADP + in the liver cytosol is generally around 100:1 citation needed ] . This makes the cytosol a highly reducing environment. One NADPH-using pathway creates NADP + , which stimulates glucose-6-phosphate dehydrogenase to produce more NADPH. This step is also inhibited by acetyl CoA. citation needed ]

G6PD activity is also post-translationally regulated by the cytoplasmic deacetylase SIRT2. SIRT2-mediated deacetylation and activation of G6PD stimulates the oxidative branch of PPP to counter oxidative damage or to supply cytosolic NADPH to support de novo lipogenesis.


Several deficiencies in the level of activity (not function) of glucose-6-phosphate dehydrogenase have been observed to be associated with resistance to the malaria 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 parasite life cycle long enough for productive growth.

What are the products of the pentose phosphate pathway?

The pentose phosphate pathway occurs in the cytosol of the cell, a site similar to glycolysis. The two most important products from this process are the ribose-5-phosphate sugar used to make DNA and RNA, and the NADPH molecule that helps build other molecules.