Pentose phosphate pathway

You don't need to be Editor-In-Chief to add or edit content to WikiDoc. You can begin to add to or edit text on this WikiDoc page by clicking on the edit button at the top of this page. Next enter or edit the information that you would like to appear here. Once you are done editing, scroll down and click the Save page button at the bottom of the page.

WikiDoc Resources for Pentose phosphate pathway
Articles
Most recent articles on Pentose phosphate pathway Most cited articles on Pentose phosphate pathway Review articles on Pentose phosphate pathway Articles on Pentose phosphate pathway in N Eng J Med, Lancet, BMJ
Media
Powerpoint slides on Pentose phosphate pathway Images of Pentose phosphate pathway Photos of Pentose phosphate pathway Podcasts & MP3s on Pentose phosphate pathway Videos on Pentose phosphate pathway
Evidence Based Medicine
Cochrane Collaboration on Pentose phosphate pathway Bandolier on Pentose phosphate pathway TRIP on Pentose phosphate pathway
Clinical Trials
Ongoing Trials on Pentose phosphate pathway at Clinical Trials.gov Trial results on Pentose phosphate pathway Clinical Trials on Pentose phosphate pathway at Google
Guidelines / Policies / Govt
US National Guidelines Clearinghouse on Pentose phosphate pathway NICE Guidance on Pentose phosphate pathway NHS PRODIGY Guidance FDA on Pentose phosphate pathway CDC on Pentose phosphate pathway
Books
Books on Pentose phosphate pathway
News
Pentose phosphate pathway in the news Be alerted to news on Pentose phosphate pathway News trends on Pentose phosphate pathway
Commentary
Blogs on Pentose phosphate pathway
Definitions
Definitions of Pentose phosphate pathway
Patient Resources / Community
Patient resources on Pentose phosphate pathway Discussion groups on Pentose phosphate pathway Patient Handouts on Pentose phosphate pathway Directions to Hospitals Treating Pentose phosphate pathway Risk calculators and risk factors for Pentose phosphate pathway
Healthcare Provider Resources
Symptoms of Pentose phosphate pathway Causes & Risk Factors for Pentose phosphate pathway Diagnostic studies for Pentose phosphate pathway Treatment of Pentose phosphate pathway
Continuing Medical Education (CME)
CME Programs on Pentose phosphate pathway
International
Pentose phosphate pathway en Espanol Pentose phosphate pathway en Francais
Business
Pentose phosphate pathway in the Marketplace Patents on Pentose phosphate pathway
Experimental / Informatics
List of terms related to Pentose phosphate pathway

Please Take Over This Page and Apply to be Editor-In-Chief for this topic: There can be one or more than one Editor-In-Chief. You may also apply to be an Associate Editor-In-Chief of one of the subtopics below. Please mail us [1] to indicate your interest in serving either as an Editor-In-Chief of the entire topic or as an Associate Editor-In-Chief for a subtopic. Please be sure to attach your CV and or biographical sketch.

The pentose phosphate pathway (also called Phosphogluconate Pathway, or Hexose Monophosphate Shunt [HMP shunt]) is a 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. For most organisms it takes place in the cytosol; in plants most steps take place in plastids.^[1]

Uses

The primary functions of the pathway are:

• To generate reducing equivalents, in the form of NADPH, for reductive biosynthesis reactions within cells.
• To provide the cell with ribose-5-phosphate (R5P) for the synthesis of the nucleotides and nucleic acids.
• Although not a significant function of the PPP, it can operate to metabolize dietary pentose sugars derived from the digestion of nucleic acids as well as to rearrange the carbon skeletons of dietary carbohydrates into glycolytic/gluconeogenic intermediates.

Located exclusively in the cytoplasm, 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.

Significantly, erythrocytes utilize the reactions of the PPP to generate large amounts of NADPH used in the reduction of glutathione

It is also used to generate hydrogen peroxide for phagocytes.^[2]

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-phosphogluconolactonase	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
ribose 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 a NADPH-utilizing pathway, thus, stimulates production of more NADPH.

See also

• G6PDH deficiency - A hereditary disease that disrupts the pentose phosphate pathway
• NADPH
• RNA
• thiamine deficiency

Erythrocytes and the Pentose Phosphate Pathway

The predominant pathways of carbohydrate metabolism in the red blood cell (RBC) are glycolysis, the PPP and 2,3-bisphosphoglycerate (2,3-BPG) metabolism (refer to discussion of hemoglobin for review of role of 2,3-BPG). Glycolysis provides ATP for membrane ion pumps and NADH for re-oxidation of methemoglobin. The PPP supplies the RBC with NADPH to maintain the reduced state of glutathione. The inability to maintain reduced glutathione in RBCs leads to increased accumulation of peroxides, predominantly H₂O₂, that in turn results in a weakening of the cell membrane and concomitant hemolysis. Accumulation of H₂O₂ also leads to increased rates of oxidation of hemoglobin to methemoglobin that also weakens the cell wall. Glutathione removes peroxides via the action of glutathione peroxidase. The PPP in erythrocytes is essentially the only pathway for these cells to produce NADPH. Any defect in the production of NADPH could, therefore, have profound effects on erythrocyte survival.

Several deficiencies in the level of activity (not function) of glucose-6-phosphate dehydrogenase have been observed to be associated with resistance to the malarial parasite, Plasmodium falciparum, among individuals of Mediterranean and African descent. The basis for this resistance is the weakening of the red cell membrane (the erythrocyte is the host cell for the parasite) such that it cannot sustain the parasitic life cycle long enough for productive growth.^[3]

References

1. ↑ Kruger NJ, von Schaewen A (June 2003). "The oxidative pentose phosphate pathway: structure and organisation". Curr. Opin. Plant Biol. 6 (3): 236–46. PMID 12753973.
2. ↑ Immunology at MCG 1/cytotox
3. ↑ Pentose Phosphate Pathway

External links

• The chemical logic behind the pentose phosphate pathway
• MeSH Pentose+Phosphate+Pathway
• http://www.bioon.com/book/biology/mwking/pentose-phosphate-pathway.html

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

v • d • e Pentose phosphate pathway metabolic intermediates
Oxidative	6-Phosphogluconolactone - 6-Phosphogluconate - Ribulose 5-phosphate - Ribose 5-phosphate
Nonoxidative	Xylulose 5-phosphate - Sedoheptulose 7-phosphate - Erythrose 4-phosphate
see also enzymes

v • d • e WikiDoc Research Resources for Pentose phosphate pathway
Articles on Pentose phosphate pathway	Most recent articles on Pentose phosphate pathway • Most cited articles on Pentose phosphate pathway • Review articles on Pentose phosphate pathway • Articles on Pentose phosphate pathway in N Eng J Med, Lancet, BMJ
Media (Slides, Video, Images, MP3) on Pentose phosphate pathway	Powerpoint slides on Pentose phosphate pathway • Images of Pentose phosphate pathway • Photos of Pentose phosphate pathway • Podcasts & MP3s on Pentose phosphate pathway • Videos on Pentose phosphate pathway
Evidence Based Medicine Regarding Pentose phosphate pathway	Cochrane Collaboration on Pentose phosphate pathway • Bandolier on Pentose phosphate pathway • TRIP on Pentose phosphate pathway
Cost Effectiveness of Pentose phosphate pathway	Cost Effectiveness of Pentose phosphate pathway
Clinical Trials Involving Pentose phosphate pathway	Ongoing Trials on Pentose phosphate pathway at Clinical Trials.gov • Trial results on Pentose phosphate pathway • Clinical Trials on Pentose phosphate pathway at Google
Guidelines / Policies / Government Resources (FDA/CDC) Regarding Pentose phosphate pathway	US National Guidelines Clearinghouse on Pentose phosphate pathway • NICE Guidance on Pentose phosphate pathway • NHS PRODIGY Guidance • FDA on Pentose phosphate pathway • CDC on Pentose phosphate pathway
Textbook Information on Pentose phosphate pathway	Books and Textbook Information on Pentose phosphate pathway
Pharmacology Resources on Pentose phosphate pathway	Dosing of Pentose phosphate pathway • Drug interactions with Pentose phosphate pathway • Side effects of Pentose phosphate pathway • Allergic reactions to Pentose phosphate pathway • Overdose information on Pentose phosphate pathway • Carcinogenicity information on Pentose phosphate pathway • Pentose phosphate pathway in pregnancy • Pharmacokinetics of Pentose phosphate pathway •
Genetics, Pharmacogenomics, and Proteinomics of Pentose phosphate pathway	Genetics of Pentose phosphate pathway • Pharmacogenomics of Pentose phosphate pathway • Proteomics of Pentose phosphate pathway
Newstories on Pentose phosphate pathway	Pentose phosphate pathway in the news • Be alerted to news on Pentose phosphate pathway • News trends on Pentose phosphate pathway
Commentary on Pentose phosphate pathway	Blogs on Pentose phosphate pathway
Patient Resources on Pentose phosphate pathway	Patient resources on Pentose phosphate pathway • Discussion groups on Pentose phosphate pathway • Patient Handouts on Pentose phosphate pathway • Directions to Hospitals Treating Pentose phosphate pathway • Risk calculators and risk factors for Pentose phosphate pathway
Healthcare Provider Resources on Pentose phosphate pathway	Symptoms of Pentose phosphate pathway • Causes & Risk Factors for Pentose phosphate pathway • Diagnostic studies for Pentose phosphate pathway • Treatment of Pentose phosphate pathway
Continuing Medical Education (CME) Programs on Pentose phosphate pathway	CME Programs on Pentose phosphate pathway
International Resources on Pentose phosphate pathway	Pentose phosphate pathway en Espanol • Pentose phosphate pathway en Francais
Business Resources on Pentose phosphate pathway	Pentose phosphate pathway in the Marketplace • Patents on Pentose phosphate pathway
Informatics Resources on Pentose phosphate pathway	List of terms related to Pentose phosphate pathway

cs:Pentosofosfátový cyklus

de:Pentosephosphatwegit:Via dei pentoso fosfati he:מסלול הפנטוז פוספטmk:Пентозо-фосфатен пат no:Pentosefosfatshuntensv:Pentosfosfatvägen