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.

1st -Ribulose 5-phosphate 3-epimerase alters the configuration about carbon 3,

forming the epimer xylulose 5-phosphate, also a ketopentose.

2nd -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 Mg2+ and thiamin diphosphate (vitamin B1) 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 CO2 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