PENTOSE PHOSPHATE PATHWAY

The pentose phosphate pathway (PPP) is the major source for NADPH that is strongly required for anabolic processes. Because of its structure, NADPH readily donates hydrogen ions to metabolites thus reducing them and making them available for energy harvest at a later time.

The beginning molecule in PPP is glucose-6-P which is the second intermediate metabolite in glycolysis. Glucose-6-P is oxidized in the presence of glucose-6-P dehydrogenase (G6PD) and NADP+.  This step is highly regulated.  NADPH and fatty acyl-CoA are strong negative G6PD inhibitors that will decrease NADPH production when concentrations are high or when fatty acids synthesis is no longer necessary.

The metabolic product of this step is gluconolactone which is particularly unstable. Gluconolactonase causes gluconolactone to undergo a ring opening hydrolysis that generates a more stable acid sugar, 6-phospho-D-gluconate. 6-phospho-D-gluconate is oxidized by NADP+ in the presence of 6-phosphogluconate dehydrogenase (PGD) which yields ribulose-5-phosphate.

This oxidation phase that generates NADPH is then followed by an isomerization phase. Ribulose-5-phosphate can be isomerized by ribose-5P isomerase (RPIA) to produce ribose-5-phosphate, one of the main building blocks of nucleic acids.

ppp-off

If production of ribose-5-phosphate exceeds the common needs in the organism, then ribulose-5P-3-epimerase catalyzes a chirality rearrangement about the center carbon creating xylulose-5-phosphate.

The third part of the PPP is a rearrangement phase. Either ribose-5-phosphate or xylulose-5-phosphate can then be rearranged to produce many different length carbon through action of two main enzymes:

Transaldolase (TALDO1) cleaves a three carbon unit from sedoheptulose-7-P and adds this three carbon unit to glyceraldehyde-3-P thus resulting in erythrose-4-P and fructose-6-P.

– Transketolase (TKT) cleaves a two carbon unit from xylulose-5-P and adds that two carbon unit to ribose-5-P thus resulting in glyceraldehyde-3-P and sedoheptulose-7-P. It can add the two carbon unit to erythrose-4-P thus resulting in glyceraldehyde-3-P and fructose-6-P.

Each of the different length resulting sugars which can be fed into many other metabolic processes (fructose-6-P and glyceraldehyde-3-P are part of the glycolysis/gluconeogenesis pathways).