The chemical logic behind... the Pentose-phosphate Pathway

Prof. Doutor Pedro Silva

Associate Professor, Universidade Fernando Pessoa


Other metabolic pathways:

In order to perform its anabolism, a cell needs not only energy (ATP): it also needs reducing power, under the form of NADPH. NADPH can be produced during glucose-6-P oxidation through a pathway distinct from glycolysis, the pentose-phosphate pathway. This pathway is very active in tissues involved in cholesterol and fatty acid (liver, adipose tissues, adrenal cortex, mammal glands). This pathway also produces ribose-5-P, the component sugar of nucleic acids.

Glucose-6-P's first carbon is first oxidized to a lactone (a cyclic carboxylic acid). Two electrons are released in this oxidation, and reduce one molecule of NADP+ to NADPH. The ring is then open by reacting with water:

Gluconate decarboxylation releases two more electrons, which reduce another NADP+ molecule. A five-carbon sugar, ribulose-5-phosphate, is produced in the reaction. By isomerization, ribulose-5-P is transformed in ribose-5-P. (In the figure, differences between both isomers are highlighted in green).

What will happen next depends on the needs of the cell: if its needs for NADPH outweigh those for ribose-5-P, its carbon atoms can be "recycled". This proceeds through three reactions, which form the non-oxidative part ot the pentose-phosphate pathway. In the first reaction, ribose-5-P will accept two carbon atoms from xylulose-5-P (obtained by epimerization of ribulose-5-P), yielding sedoheptulose-7-P and glyceraldehyde-3-P:

Sedoheptulose-7-P transfers three carbons to glyceraldehyde-3-P, yielding fructose-6-P and erythrose-4-P:

Erythrose-4-P then accepts two carbon atoms from a second molecule of xylulose-5-P, yielding a second molecul of fructose-6-P and a glyceraldehyde-3-P molecule:

The balance of these three reactions is:

2 xylulose-5-P + ribose-5-P -----> 2 fructose-6-P + glyceraldehyde-3-P

Fructose-6-P and glyceraldehyde-3-P can be degraded by glycolysis in orer to produce energy, or recycled through gluconeogenesis to regenerate glucose-6-P. In the latter case, through six consecutive cycles of the pentose-phosphate pathway and gluconeogenesis one glucose-6-P molecule can be completely oxidized to six CO2 molecules, with concommitant production of 12 NADPH molecules. When the demand for ribose-5-P is larger than tyhe demand for NADPH, the non-oxidative part of the pentose-phosphate pathway can operate "in reverse", yielding three ribose-5-P from two fructose-6-P and one glyceraldehyde-3-P.

Further reading

cover Biochemistry, by Donald Voet & Judith Voet

An excellent text. It presents Biochemistry with frequent references to organic chemistry and biochemical logic. Highly reccommended for students of Biochemistry, Chemistry and Pharmaceutical Sciences.

cover Biochemistry, Stryer

A widely used classical text, frequently updated and re-issued.

cover Textbook of Biochemistry with Clinical Correlations, Thomas Devlin

Strongly advised to students in Nursing, Medicine, Dentistry, etc. Plenty of examples of application of biochemical knowledge to clinical cases.

cover Principles of Biochemistry, Lehninger

A widely used classical text, frequently updated and re-issued.