What is Pentose Phosphate Pathway?

While glucose metabolism by glycolysis occurs where energy is needed quickly, e.g. in brain and muscle cells, a second pathway for glucose metabolism, called pentose phosphate pathway, operates in tissues that synthesize fatty acids and steroids (Figure 1).

Pentose Phosphate Pathway

Figure 1. Pentose Phosphate Pathway.

As in glycolysis, glucose is phosphorylated at the 6-position to give glucose-6-phosphate (1).

NADP-dependent oxidation at the anomeric center is catalyzed by glucose-6-phosphate dehydrogenase and yields 6-phosphogluconolactone (2), which upon hydrolysis yields the 6-phosphogluconate (3).

Another NADP-dependent oxidation at the C3-hydroxy group transforms 6-phosphogluconate to ribulose-5-phosphate (4).

Tautomerization leads to either xylulose-5-phosphate (6) formation catalyzed by ribulose-5-phosphate epimerase or to ribose-5- phosphate (5) formation, which is catalyzed by ribulose-5- phosphate isomerase.

Growing and dividing cells require ribose-5-phosphate, but excess ribose-5-phosphate (5) reacts with xylulose-5-phosphate (6), a reaction catalyzed by transketolase, which leads to glyceraldehyde- 3-phosphate (8) and sedoheptulose-7-phosphate (7) as products.

In the next step, the transaldolase-catalyzed reaction of sedoheptulose- 7-phosphate (7) with glyceraldehydes-3-phosphate (8) yields erythrose-4-phosphate (9) and fructose-6-phosphate (11).

One closing step of this pathway involves again xylulose-5- phosphate (6) and erythrose-4-phosphate (9), but in this step the transketolase-catalyzed two-carbon unit transfer gives fructose-6- phosphate (11) and D-glyceraldehyde-3-phosphate (8).

An additional link between D-glyceraldehyde-3-phosphate (8) and fructose-6-phosphate is channelled through fructose-1,6- bisphosphate (10).