the pentose phosphate pathway. introduction the enzymes of the pentose phosphate pathway are present...

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