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a trodden path (同)footpath
taking place in the presence of oxygen; "oxidative glycolysis"; "oxidative rancidity"

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/09/06 10:23:58」(JST)

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The Pentose Phosphate Pathway

In biochemistry, the pentose phosphate pathway (also called the phosphogluconate pathway and the hexose monophosphate shunt) is a metabolic pathway parallel to glycolysis that generates NADPH and pentoses (5-carbon sugars) as well as Ribose 5-phosphate, a precursor for the synthesis of nucleotides. While it does involve oxidation of glucose, its primary role is anabolic rather than catabolic.

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. For most organisms, the pentose phosphate pathway takes place in the cytosol; in plants, most steps take place in plastids.^[1]

Similar to glycolysis, the pentose phosphate pathway appears to have a very ancient evolutionary origin. The reactions of this pathway are mostly enzyme-catalyzed in modern cells, however, they also occur non-enzymatically under conditions that replicate those of the Archean ocean, and are catalyzed by metal ions, particularly ferrous ions (Fe(II)).^[2] This suggests that the origins of the pathway could date back to the prebiotic world.

Outcome

The primary results of the pathway are:

The generation of reducing equivalents, in the form of NADPH, used in reductive biosynthesis reactions within cells (e.g. fatty acid synthesis).
Production of ribose 5-phosphate (R5P), used in the synthesis of nucleotides and nucleic acids.
Production of erythrose 4-phosphate (E4P) used in the synthesis of aromatic amino acids.

Aromatic amino acids, in turn, are precursors for many biosynthetic pathways, including the lignin in wood.^{[citation needed]}

Dietary pentose sugars derived from the digestion of nucleic acids may be metabolized through the pentose phosphate pathway, and the carbon skeletons of dietary carbohydrates may be converted into glycolytic/gluconeogenic intermediates.

In mammals, the PPP occurs exclusively in the cytoplasm, and is found to be most active in the liver, mammary gland and adrenal cortex in the human.^{[citation needed]} The PPP is one of the three main ways the body creates molecules with reducing power, accounting for approximately 60% of NADPH production in humans.^{[citation needed]}

One of the uses of NADPH in the cell is to prevent oxidative stress. It reduces glutathione via glutathione reductase, which converts reactive H₂O₂ into H₂O by glutathione peroxidase. If absent, the H₂O₂ would be converted to hydroxyl free radicals by Fenton chemistry, which can attack the cell. Erythrocytes, for example, generate a large amount of NADPH through the pentose phosphate pathway to use in the reduction of glutathione.

Hydrogen peroxide is also generated for phagocytes in a process often referred to as a respiratory burst.^[3]

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.

Oxidative phase of pentose phosphate pathway.

Glucose-6-phosphate (1), 6-phosphoglucono-δ-lactone (2), 6-phosphogluconate (3), ribulose 5-phosphate (4)

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 hydroxyl on carbon 1 of glucose 6-phosphate turns into a carbonyl, 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.

The overall reaction for this process is:

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

Non-oxidative phase

The pentose phosphate pathway's nonoxidative phase

Reactants	Products	Enzymes
ribulose 5-phosphate	→ ribose 5-phosphate	Ribulose 5-Phosphate Isomerase
ribulose 5-phosphate	→ xylulose 5-phosphate	Ribulose 5-Phosphate 3-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

Net reaction: 3 ribulose-5-phosphate → 1 ribose-5-phosphate + 2 xylulose-5-phosphate → 2 fructose-6-phosphate + glyceraldehyde-3-phosphate

Regulation

Glucose-6-phosphate dehydrogenase is the rate-controlling enzyme of this pathway. It is allosterically stimulated by NADP⁺ and strongly inhibited by NADPH.^[4] The ratio of NADPH:NADP⁺ is normally about 100:1 in liver cytosol^{[citation needed]}. This makes the cytosol a highly-reducing environment. An NADPH-utilizing pathway forms NADP⁺, which stimulates Glucose-6-phosphate dehydrogenase to produce more NADPH. This step is also inhibited by acetyl CoA.^{[citation needed]}

G6PD activity is also post-translationally regulated by cytoplasmic deacetylase SIRT2. SIRT2-mediated deacetylation and activation of G6PD stimulates oxidative branch of PPP to supply cytosolic NADPH to counteract oxidative damage or support de novo lipogenesis.^[5]^[6]

Erythrocytes and the pentose phosphate pathway

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 may be a 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.^[7]

References

^ Kruger, Nicholas J; von Schaewen, Antje (June 2003). "The oxidative pentose phosphate pathway: structure and organisation". Current Opinion in Plant Biology. 6 (3): 236–246. doi:10.1016/S1369-5266(03)00039-6. Retrieved 23 February 2015.
^ Keller, Markus A.; Turchyn, Alexandra V.; Ralser, Markus (25 April 2014). "Non-enzymatic glycolysis and pentose phosphate pathway-like reactions in a plausible Archean ocean". Molecular Systems Biology. 10 (4): 725–725. doi:10.1002/msb.20145228. PMC 4023395. PMID 24771084. Retrieved 23 February 2015.
^ Immunology at MCG 1/cytotox
^ Voet Donald; Voet Judith G (2011). Biochemistry (4th ed.). p. 894. ISBN 978-0470-57095-1.
^ Wang YP, Zhou LS, Zhao YZ, Wang SW, Chen LL, Liu LX, Ling ZQ, Hu FJ, Sun YP, Zhang JY, Yang C, Yang Y, Xiong Y, Guan KL, Ye D (June 2014). "Regulation of G6PD acetylation by SIRT2 and KAT9 modulates NADPH homeostasis and cell survival during oxidative stress". EMBO Journal. 33: 1304–20. doi:10.1002/embj.201387224. PMID 24769394.
^ Xu SN, Wang TS, Li X, Wang YP (Sep 2016). "SIRT2 activates G6PD to enhance NADPH production and promote leukaemia cell proliferation". Sci Rep. 6: 32734. doi:10.1038/srep32734. PMID 27586085.
^ Cappadoro M, Giribaldi G, O'Brien E, et al. (October 1998). "Early phagocytosis of glucose-6-phosphate dehydrogenase (G6PD)-deficient erythrocytes parasitized by Plasmodium falciparum may explain malaria protection in G6PD deficiency". Blood. 92 (7): 2527–34. PMID 9746794.

External links

The chemical logic behind the pentose phosphate pathway
Pentose Phosphate Pathway at the US National Library of Medicine Medical Subject Headings (MeSH)
Pentose phosphate pathway Map - Homo sapiens

UpToDate Contents

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1. ヘキソースリン酸側路およびグルタチオン代謝疾患（グルコース-6-リン酸脱水素酵素欠損症を除く） disorders of the hexose monophosphate shunt and glutathione metabolism other than glucose 6 phosphate dehydrogenase deficiency
2. 筋肉におけるエネルギー代謝 energy metabolism in muscle
3. 視神経膠腫 optic pathway glioma
4. Hemolytic anemia due to drugs and toxins
5. パーキンソン病の病因および発症機序 etiology and pathogenesis of parkinson disease

English Journal

Defects in Peroxisomal 6-Phosphogluconate Dehydrogenase Isoform PGD2 Prevent Gametophytic Interaction in Arabidopsis thaliana.

Hölscher C1, Lutterbey MC1, Lansing H1, Meyer T1, Fischer K1, von Schaewen A2.
Plant physiology.Plant Physiol.2016 May;171(1):192-205. doi: 10.1104/pp.15.01301. Epub 2016 Mar 3.
We studied the localization of 6-phosphogluconate dehydrogenase (PGD) isoforms of Arabidopsis (Arabidopsis thaliana). Similar polypeptide lengths of PGD1, PGD2, and PGD3 obscured which isoform may represent the cytosolic and/or plastidic enzyme plus whether PGD2 with a peroxisomal targeting motif al
PMID 26941195

Improving ethanol yield in acetate-reducing Saccharomyces cerevisiae by cofactor engineering of 6-phosphogluconate dehydrogenase and deletion of ALD6.

Papapetridis I1, van Dijk M1, Dobbe AP1, Metz B1, Pronk JT1, van Maris AJ2.
Microbial cell factories.Microb Cell Fact.2016 Apr 26;15(1):67. doi: 10.1186/s12934-016-0465-z.
BACKGROUND: Acetic acid, an inhibitor of sugar fermentation by yeast, is invariably present in lignocellulosic hydrolysates which are used or considered as feedstocks for yeast-based bioethanol production. Saccharomyces cerevisiae strains have been constructed, in which anaerobic reduction of acetic
PMID 27118055

Methionine Metabolism Alters Oxidative Stress Resistance via the Pentose Phosphate Pathway.

Campbell K1, Vowinckel J1, Keller MA1, Ralser M1,2.
Antioxidants & redox signaling.Antioxid Redox Signal.2016 Apr 1;24(10):543-7. doi: 10.1089/ars.2015.6516. Epub 2016 Mar 15.
Nutrient uptake and metabolism have a significant impact on the way cells respond to stress. The amino acid methionine is, in particular, a key player in the oxidative stress response, and acting as a reactive oxygen species scavenger, methionine is implicated in caloric restriction phenotypes and a
PMID 26596469

Japanese Journal

Effects of edd and pgi Disruptions on Inosine Accumulation in Escherichia coli

Shimaoka Megumi,Kawasaki Hisashi,Takenaka Yasuhiro [他],KURAHASHI Osamu,MATSUI Hiroshi
Bioscience, biotechnology, and biochemistry 69(7), 1248-1255, 2005-07-23
… Sodium gluconate instead of glucose was tested as a carbon source to increase the supply of ribose-5-phosphate through the oxidative pentose phosphate pathway. … (6-phosphogluconate dehydrase gene)-disrupted mutant accumulated 2.5 g/l of inosine from 48 g/l of sodium gluconate, compared with 1.4 g/l of inosine in the <I>edd</I> …
NAID 130000030263

Coenzyme Specificity of Enzymes in the Oxidative Pentose Phosphate Pathway of Gluconobacter oxydans(Microbiology & Fermentation Technology)

Tonouchi Naoto,Sugiyama Masakazu,Yokozeki Kenzo
Bioscience, biotechnology, and biochemistry 67(12), 2648-2651, 2003-12-23
… The coenzyme specificity of enzymes in the oxidative pentose phosphate pathway of Gluconobacter oxydans was investigated. … By investigation of the activities of glucose-6-phosphate dehydrogenase (G6PDH) and 6-phosphogluconate dehydrogenase (6PGDH) in the soluble fraction of G. … It was suggested that the pentose phosphate pathway is responsible for NADH regeneration in G.oxydans. …
NAID 110002694033

Characterization of a Flavinogenic Mutant of Methanol Yeast Candida boidinii and Its Extracellular Secretion of Riboflavin

Suryadi Herman,Yoshida Nobuyuki,Yamada-Onodera Keiko [他],KATSURAGI TOHORU,TANI YOSHIKI
Journal of bioscience and bioengineering 90(1), 52-56, 2000-07-25
… The mutant was defective in the oxidative pentose phosphate pathway, lacking glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase. … These high activities might direct the flux of the carbon source to the nonoxidative pathway with formation of a large amount of pentose phosphates, increasing riboflavin synthesis. …
NAID 110002684611

「ペントースリン酸経路」

　　[★]

英: pentose phosphate pathway, PPP, pentose phosphate cycle
同: 五炭糖リン酸回路、ヘキソース一リン酸回路 hexose monophosphate pathway、hexose monophosphate shunt HMP shunt、ワールブルグ・ディケンズ経路ワーブルグ・ディッケンズ経路 Warburg-Dickens pathway、ホスホグルコン酸経路？？ phosphogluconate oxidative pathway？？
関: 解糖系

NADPHとリボース5-リン酸を産生する経路

臨床関連

グルコース-6-リン酸脱水素酵素欠損症 G6PD欠損症

グルコース6-リン酸脱水素酵素 glucose-6-phosphate dehydrogenase

「pathway」

　　[★]

経路、パスウェイ

関: route

「oxidative」

　　[★]

酸化的な

関: oxidatively

[1] Kruger, Nicholas J; von Schaewen, Antje (June 2003). "The oxidative pentose phosphate pathway: structure and organisation". Current Opinion in Plant Biology. 6 (3): 236–246. doi:10.1016/S1369-5266(03)00039-6. Retrieved 23 February 2015.

[2] Keller, Markus A.; Turchyn, Alexandra V.; Ralser, Markus (25 April 2014). "Non-enzymatic glycolysis and pentose phosphate pathway-like reactions in a plausible Archean ocean". Molecular Systems Biology. 10 (4): 725–725. doi:10.1002/msb.20145228. PMC 4023395. PMID 24771084. Retrieved 23 February 2015.

[3] Immunology at MCG 1/cytotox

[4] Voet Donald; Voet Judith G (2011). Biochemistry (4th ed.). p. 894. ISBN 978-0470-57095-1.

[5] Wang YP, Zhou LS, Zhao YZ, Wang SW, Chen LL, Liu LX, Ling ZQ, Hu FJ, Sun YP, Zhang JY, Yang C, Yang Y, Xiong Y, Guan KL, Ye D (June 2014). "Regulation of G6PD acetylation by SIRT2 and KAT9 modulates NADPH homeostasis and cell survival during oxidative stress". EMBO Journal. 33: 1304–20. doi:10.1002/embj.201387224. PMID 24769394.

[Xu_2016-6] Xu SN, Wang TS, Li X, Wang YP (Sep 2016). "SIRT2 activates G6PD to enhance NADPH production and promote leukaemia cell proliferation". Sci Rep. 6: 32734. doi:10.1038/srep32734. PMID 27586085.

[7] Cappadoro M, Giribaldi G, O'Brien E, et al. (October 1998). "Early phagocytosis of glucose-6-phosphate dehydrogenase (G6PD)-deficient erythrocytes parasitized by Plasmodium falciparum may explain malaria protection in G6PD deficiency". Blood. 92 (7): 2527–34. PMID 9746794.

v t e Metabolism: carbohydrate metabolism · pentose phosphate pathway enzymes

oxidative	Glucose-6-phosphate dehydrogenase 6-phosphogluconolactonase Phosphogluconate dehydrogenase

nonoxidative	Phosphopentose isomerase Phosphopentose epimerase Transketolase Transaldolase

v t 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

リンク元	「ペントースリン酸経路」
関連記事	「pathway」「oxidative」

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案内

案内

phosphogluconate oxidative pathway