The Pentose Phosphate Pathway

Introduction the enzymes of the pentose phosphate pathway are present in cytosol. The sequence of reactions of the pathway may be divided into two phases: an oxidative nonreversible phase and a nonoxidative reversible phase

Overview In first phase, glucose 6-phosphate undergoes dehydrogenation and decarboxylation to yield a pentose, ribulose 5-phosphate. In second phase, ribulose 5-phosphate is converted back to glucose 6-phosphate by a series of reactions involving mainly two enzymes: transketolase and transaldolase

Importance It is an alternative route for the metabolism of glucose. It does not lead to formation of ATP it has two major functions: (1) The synthesis of ribose for nucleotide and nucleic acid formation and (2) The formation of NADPH for synthesis of fatty acids and steroids

Dehydrogenation of glucose 6- phosphate to 6-phosphogluconate catalyzed by glucose 6-phosphate dehydrogenase, an NADP-dependent enzyme. The hydrolysis of 6- phosphogluconolactone is accomplished by the enzyme gluconolactone hydrolase.

A second oxidative step is catalyzed by 6-phosphogluconate dehydrogenase, which also requires NADP + as hydrogen acceptor. Decarboxylation follows with the formation of the ketopentose ribulose 5-phosphate

Ribulose 5-phosphate is the substrate for two enzymes. 1 st -Ribulose 5-phosphate 3-epimerase alters the configuration about carbon 3, forming the epimer xylulose 5-phosphate, also a ketopentose. 2 nd -Ribose 5-phosphate ketoisomerase converts ribulose 5-phosphate to the corresponding aldopentose, ribose 5-phosphate ribose 5-phosphate is the precursor of the ribose required for nucleotide and nucleic acid synthesis.

Transketolase transfers the two- carbon unit comprising carbons 1 and 2 of a ketose onto the aldehyde carbon of an aldose sugar. the conversion of a ketose sugar into an aldose with two carbons less and an aldose sugar into a ketose with two carbons more.

The reaction requires Mg 2+ and thiamin diphosphate (vitamin B 1 ) as coenzyme. The two-carbon moiety transferred is probably glycolaldehyde bound to thiamin diphosphate.

Thus, transketolase catalyzes the transfer of the two-carbon unit from xylulose 5-phosphate to ribose 5- phosphate, producing the seven- carbon ketose sedoheptulose 7- phosphate and the aldose glyceraldehyde 3- phosphate.

Transaldolation- Transaldolase catalyzes the transfer of a three-carbon dihydroxyacetone moiety (carbons 1–3) from the ketose sedoheptulose 7- phosphate onto the aldose glyceraldehyde 3-phosphate to form the ketose fructose 6-phosphate and the four-carbon aldose erythrose 4- phosphate.

transketolase, xylulose 5-phosphate serves as a donor of glycolaldehyde. In this case erythrose 4-phosphate is the acceptor, and the products of the reaction are fructose 6-phosphate and glyceraldehyde 3-phosphate.

In order to oxidize glucose completely to CO 2 via the pentose phosphate pathway, there must be enzymes present in the tissue to convert glyceraldehyde 3- phosphate to glucose 6-phosphate. This involves reversal of glycolysis and the gluconeogenic enzyme fructose 1,6- bisphosphatase