The Pentose Phosphate Pathway

The pentose phosphate pathway is a key pathway in metabolism that is used to synthesize nucleotides  NADPH and pentose sugars such as ribose-5-phosphate. It can also be used to generate other pentoses which are 5-carbon sugars.

We also know the pentose phosphate pathway as the phosphogluconate pathway or the hexose monophosphate shunt. 

The pathway parallels glycolysis and whilst it requires oxidation of glucose it is a primarily an anabolic not catabolic pathway because it generates precursors for nucleotide synthesis. The net energy use in the pathway is positive. It is especially important in erythrocytes (red blood cells).

The pathway is only found in the cytoplasm of live cells (hepatocytes), the adrenal cortex and in lactating mammary glands – i.e. in animals. It does occur in the plastids of plants.

The Objective of the Pathway

The pentose phosphate pathway is an alternative route for glucose oxidation and most importantly does not consume ATP. It is necessary for producing NADPH that can be used in fatty acid synthesis. In this situation, the 3-carbon sugar, glyceraldehyde-3-phosphate and the sugar fructose-6-phosphate are generated in this pathway and can reenter the glycolysis pathway.

NADPH is also needed for reducing the antioxidant glutathione. It functions by protecting cells from the damage caused by free radicals such as peroxides. Glutathione is used to transport amino acids across cell membranes of some cells using the gamma-glutamyl cycle.

The pathway starts with glucose-6-phosphate which is usually derived from glucose.

It has two distinct phases:-

1. the oxidative phase where NADPH is generated
2. the non-oxidative phase which is the synthesis of 5-carbon sugars

As with glycolysis, glucose is transported into the cell cytoplasm. It is converted using the enzyme hexokinase to glucose-6-phosphate. This is driven by hydrolysis of ATP to ADP. The glucose-6-phosphate can either be used in glycolysis to generate pyruvate or it can follow the pentose phosphate pathway

The Oxidative Phase

Glucose-6-phosphate is converted to 6-phosphogluconolactone using the enzyme glucose-6-phosphate dehydrogenase. In the reaction, one molecule of NADP+ is reduced to NADPH. The second step is hydrolysis of the 6-phosphogluconolactone to 6-phosphogluconate, catalysed by the enzyme gluconolactonase.

The 6-phosphogluconate then undergoes oxidation then decarboxylation with the release of carbon dioxide and the generation of a second molecule of NADPH. The product is ribulose-5-phosphate. The reaction is catalysed by 6-phosphogluconate dehydrogenase. 

The Non-Oxidative Reactions

Ribulose-5-phosphate can be isomerized to ribose-5-phosphate or epimerized to xylulose-5-phosphate. These two sugars are involved in reactions catalysed by transketolase and transaldolase respectively. They generate fructose-6-phosphate and glyceraldehdye -3-phosphate respectively. Both enzymes catalyse the transfer of carbon units.

Transketolase needs thiamine pyrophosphate for the transfer of two-carbon units. Transaldolase is involved in transferring three-carbon units.