Pentose phosphate pathway

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The pentose phosphate pathway (also called Phosphogluconate Pathway, or Hexose Monophosphate Shunt [HMP shunt]) is a cytosolic process that serves to generate NADPH and the synthesis of pentose (5-carbon) sugars. There are two distinct phases in the pathway. The first is the oxidative phase, in which NADPH is generated, and the second is the non-oxidative synthesis of 5 carbon sugars. This pathway is an alternative to glycolysis. While it does involve oxidation of glucose, its primary role is anabolic rather than catabolic.

Uses

The pathway is one of the three main ways the body creates molecules with reducing power, accounting for approximately 60% of NADPH production in humans.

One of the uses of NADPH in the cell is to prevent oxidative stress. It reduces the coenzyme glutathione which converts reactive H₂O₂ into H₂O. If absent, the H₂O₂ would be converted to hydroxyl free radicals which can attack the cell.

It is also used to generate hydrogen peroxide for phagocytes.^[1]

Phases

Oxidative phase

In this phase, two molecules of NADP⁺ are reduced to NADPH, utilizing the energy from the conversion of glucose-6-phosphate into ribulose 5-phosphate.

The entire set of reactions can be summarized as follows:

Reactants	Products	Enzyme	Description
Glucose 6-phosphate + NADP+	→ 6-phosphoglucono-δ-lactone + NADPH	glucose 6-phosphate dehydrogenase	Dehydrogenation. The hemiacetal hydroxyl group located on carbon 1 of glucose 6-phosphate is converted into a carbonyl group, generating a lactone, and in the process NADPH is generated.
6-phosphoglucono-δ-lactone + H2O	→ 6-phosphogluconate + H+	6-phosphoglucolactonase	Hydrolysis
6-phosphogluconate + NADP+	→ ribulose 5-phosphate + NADPH + CO2	6-phosphogluconate dehydrogenase	Oxidative decarboxylation. NADP+ is the electron acceptor, generating another molecule of NADPH, a CO2, and ribulose 5-phosphate.
ribulose 5-phosphate	ribose 5-phosphate	Phosphopentose isomerase	Isomerization. (Can also be considered part of nonoxidative phase)

The overall reaction for this process is:

Glucose 6-phosphate + 2 NADP⁺ + H₂O → ribulose 5-phosphate + 2 NADPH + 2 H⁺ + CO₂

Non-oxidative phase

Reactants	Products	Enzymes
ribulose 5-phosphate	→ ribose 5-phosphate	phosphopentose isomerase
ribulose 5-phosphate	→ xylulose 5-phosphate	phosphopentose epimerase
xylulose 5-phosphate + ribose 5-phosphate	→ glyceraldehyde 3-phosphate + sedoheptulose 7-phosphate	transketolase
sedoheptulose 7-phosphate + glyceraldehyde 3-phosphate	→ erythrose 4-phosphate + fructose 6-phosphate	transaldolase
xylulose 5-phosphate + erythrose 4-phosphate	→ glyceraldehyde 3-phosphate + fructose 6-phosphate	transketolase

Regulation

Glucose-6-phosphate dehydrogenase is the rate controlling enzyme of this pathway. It is allosterically stimulated by NADP⁺. The ratio of NADPH:NADP⁺ is normally about 100:1 in liver cytosol. This makes the cytosol a highly reducing environment. Formation of NADP⁺ by an NADPH utilizing pathway thus stimulates production of more NADPH.

See also

• G6PDH deficiency - A hereditary disease which disrupts the pentose phosphate pathway.
• NADPH
• RNA

References

External links

• The chemical logic behind the pentose phosphate pathway
• MeSH Pentose+Phosphate+Pathway

v • d • e Metabolism: carbohydrate metabolism
Anabolism	Gluconeogenesis - Glycogenesis - Photosynthesis (Carbon fixation)
Carbohydrate catabolism	Glycolysis - Glycogenolysis - Fermentation (Ethanol, Lactic acid) - Cellular respiration - Xylose metabolism
Other	Pentose phosphate pathway

v • d • e Metabolism map

Glucuronate metabolism Pentose interconversion Inositol metabolism Cellulose and sucrose metabolism Starch and glycogen metabolism Other sugar metabolism Pentose phosphate pathway Glycolysis and Gluconeogenesis Amino sugars metabolism Small amino acid synthesis Branched amino acid synthesis Purine biosynthesis Histidine metabolism Aromatic amino acid synthesis Pyruvate decarboxylation Anaerobic respiration Fatty acid metabolism Urea cycle Aspartate amino acid group synthesis Porphyrins and corrinoids metabolism Citric acid cycle Glutamate amino acid group synthesis Pyrimidine biosynthesis  v • d • e  All pathway labels on this image are links, simply click to access the article. A high resolution labeled version of this image is available here. Image:Metabolism 790px.png

v • d • e Metabolism: carbohydrate metabolism - pentose phosphate pathway enzymes
oxidative	Glucose-6-phosphate dehydrogenase - 6-phosphogluconolactonase - Phosphogluconate dehydrogenase
nonoxidative	Phosphopentose isomerase - Phosphopentose epimerase - Transketolase - Transaldolase
see also disorders

de:Pentosephosphatwegfr:Voie des pentoses phosphates

it:Via dei pentoso fosfati he:מסלול הפנטוז פוספט ja:ペントースリン酸経路 no:Pentosefosfatshuntensv:Pentosfosfatvägen

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Acknowledgement and Attribution Regarding Sources of Content

Some of the initial content on this page may be incorporated in part from copyleft sources in the public domain including wikis such as Wikipedia and AskDrWiki. Drug information for patients came from the The National Library of Medicine. Infectious disease information may have come from the Centers for Disease Control (CDC). Differential Diagnoses are drawn from clinicians as well as an amalgamation of 3 sources: 1.The Disease Database; 2. Kahan, Scott, Smith, Ellen G. In A Page: Signs and Symptoms. Malden, Massachusetts: Blackwell Publishing, 2004:3; 3. Sailer, Christian, Wasner, Susanne. Differential Diagnosis Pocket. Hermosa Beach, CA: Borm Bruckmeir Publishing LLC, 2002:7 .