hexose monophosphate shunt

ヘキソース一リン酸回路

WordNet

1. transfer to another track, of trains
2. a conductor having low resistance in parallel with another device to divert a fraction of the current (同)electrical shunt, bypass
3. implant consisting of a tube made of plastic or rubber; for draining fluids within the body
4. a passage by which a bodily fluid (especially blood) is diverted from one channel to another; "an arteriovenus shunt"
5. provide with or divert by means of an electrical shunt
6. avoid and stay away from deliberately; stay clear of (同)eschew
7. a monosaccharide that contains six carbon atoms per molecule

PrepTutorEJDIC

1. 〈人・物〉‘を'わきにどかす;〈話題など〉‘を'他へそらす / (別の軌道に)〈車両〉‘を'入れ換える / 〈電流〉‘を'わきへそらす;〈分路〉‘を'置く / わきへそれる / 〈車両が〉分岐線に移行する / 〈U〉わきへそれること / 〈C〉転てつ器;(電気の)分路
2. …‘を'『避ける』(avoid)

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/08/23 08:26:00」(JST)

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The Pentose Phosphate Pathway

The pentose phosphate pathway (also called the phosphogluconate pathway and the hexose monophosphate shunt) is a process that generates NADPH and pentoses (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.

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, notably including the lignin in wood.

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. 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.

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.

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 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.

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
ribose 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⁺. The ratio of NADPH:NADP⁺ is normally about 100:1 in liver cytosol. 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.

See also

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

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.

References

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. グルコース-6-リン酸脱水素酵素欠損症の遺伝学および病態生理 genetics and pathophysiology of glucose 6 phosphate dehydrogenase deficiency
• 2. 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
• 3. グルコース-6-リン酸脱水素酵素欠損症の診断および治療 diagnosis and treatment of glucose 6 phosphate dehydrogenase deficiency
• 4. 薬物および毒素による外因性非自己免疫性溶血性貧血 extrinsic nonautoimmune hemolytic anemia due to drugs and toxins
• 5. メトヘモグロビン血症の遺伝学および病因 genetics and pathogenesis of methemoglobinemia

English Journal

• PFKFB3 Regulates Oxidative Stress Homeostasis via Its S-Glutathionylation in Cancer.

• Seo M1, Lee YH2.Author information 1Department of Biological Sciences, Louisiana State University, Baton Rouge, LA 70803, USA.2Department of Biological Sciences, Louisiana State University, Baton Rouge, LA 70803, USA. Electronic address: yhlee@lsu.edu.AbstractWhereas moderately increased cellular oxidative stress is supportive for cancerous growth of cells, excessive levels of reactive oxygen species (ROS) are detrimental to their growth and survival. We demonstrated that high ROS levels, via increased oxidized glutathione (GSSG), induce isoform-specific S-glutathionylation of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) at residue Cys206, which is located near the entrance to the 6-phosphofructo-2-kinase catalytic pocket. Upon this ROS-dependent, reversible, covalent modification, a marked decrease in its catalytic ability to synthesize fructose-2,6-bisphosphate (Fru-2,6-P2), the key glycolysis allosteric activator, was observed. This event was coupled to a decrease in glycolytic flux and an increase in glucose metabolic flux into the pentose phosphate pathway. This shift, in turn, caused an increase in reduced glutathione (GSH) and, ultimately, resulted in ROS detoxification inside HeLa cells. The ability of PFKFB3 to control the Fru-2,6-P2 levels in an ROS-dependent manner allows the PFKFB3-expressing cancer cells to continue energy metabolism with a reduced risk of excessive oxidative stress and, thereby, to support their cell survival and proliferation. This study provides a new insight into the roles of PFKFB3 as switch that senses and controls redox homeostasis in cancer in addition to its role in cancer glycolysis.
• Journal of molecular biology.J Mol Biol.2014 Feb 20;426(4):830-42. doi: 10.1016/j.jmb.2013.11.021. Epub 2013 Dec 1.
• Whereas moderately increased cellular oxidative stress is supportive for cancerous growth of cells, excessive levels of reactive oxygen species (ROS) are detrimental to their growth and survival. We demonstrated that high ROS levels, via increased oxidized glutathione (GSSG), induce isoform-specific
• PMID 24295899

• The bacterial Entner-Doudoroff pathway does not replace glycolysis in Saccharomyces cerevisiae due to the lack of activity of iron-sulfur cluster enzyme 6-phosphogluconate dehydratase.

• Benisch F1, Boles E2.Author information 1Institute of Molecular Biosciences, Goethe-University Frankfurt, Max-von-Laue-Str. 9, 60438 Frankfurt/Main, Germany.2Institute of Molecular Biosciences, Goethe-University Frankfurt, Max-von-Laue-Str. 9, 60438 Frankfurt/Main, Germany. Electronic address: e.boles@bio.uni-frankfurt.de.AbstractReplacement of the glycolytic pathway of Saccharomyces cerevisiae by a bacterial Entner-Doudoroff pathway (EDP) would result in lower ATP production and therefore a lower biomass yield is expected that would further allow higher products yields in the fermentation of sugars. To establish catabolism of glucose via the EDP in S. cerevisiae requires expression of only two additional enzyme activities, 6-phosphogluconate dehydratase (PGDH) and KDPG aldolase. In this work, KDPG aldolase from Escherichia coli could be successfully expressed in the yeast cytosol with very high enzyme activity. Nevertheless, simultaneous expression of KDPG aldolase and a codon optimized PGDH gene of E. coli could not replace glycolysis or the pentose phosphate pathway in growth experiments. It could be shown that this was due to the very low enzyme activity of PGDH. This bacterial enzyme is a [4Fe-4S] iron-sulfur cluster protein. Several attempts to improve the availability of iron-sulfur clusters or iron in the yeast cells, to attract the iron-sulfur cluster assembly machinery to Leu1-PGDH fusion proteins or to localize the PGDH in the mitochondria did not result in improved enzyme activities. From our results we conclude that establishing functional expression of iron-sulfur cluster enzymes will be a major task for the integration of the EDP and other biochemical pathways in yeast.
• Journal of biotechnology.J Biotechnol.2014 Feb 10;171:45-55. doi: 10.1016/j.jbiotec.2013.11.025. Epub 2013 Dec 11.
• Replacement of the glycolytic pathway of Saccharomyces cerevisiae by a bacterial Entner-Doudoroff pathway (EDP) would result in lower ATP production and therefore a lower biomass yield is expected that would further allow higher products yields in the fermentation of sugars. To establish catabolism
• PMID 24333129

• Clinical and molecular characteristics of two transaldolase-deficient patients.

• Tylki-Szymanska A, Wamelink MM, Stradomska TJ, Salomons GS, Taybert J, Dąbrowska-Leonik N, Rurarz M.Author information Department of Metabolic Diseases, The Children's Memorial Health Institute, Al. Dzieci Polskich 20, 04-730, Warsaw, Poland, atylki@op.pl.AbstractTransaldolase (TALDO) deficiency is a rare metabolic disease in the pentose phosphate pathway, which manifests as a severe, early-onset multisystem disease. The body fluids of affected patients contain increased polyol concentrations and seven-carbon chain carbohydrates. We report the molecular and clinical findings in two recently diagnosed transaldolase-deficient children, both presented at birth. During infancy, they presented thin skin with a network of visible vessels, spider telangiectasias and multiple haemangiomas. Such unusual skin changes are characteristic of liver damage. Later, the patients developed rapidly progressive nodular liver fibrosis, tubulopathy and severe clotting disturbances. The clinical features of these patients were in line with previously studied patients with transaldolase deficiency. The diagnosis was established by detecting high concentrations of erythritol, ribitol, arabitol, sedoheptitol, perseitol, sedoheptulose and sedoheptulose-7-phosphate in the urine. Detection was made by gas chromatography and liquid chromatography-tandem mass spectrometry and then confirmed by molecular analysis of the TALDO gene. Conclusion: Transaldolase deficiency, a rare early-onset multisystem disease, should be considered by neonatologists, paediatricians, hepatologists and nephrologists in the differential diagnosis of patients presenting hepatosplenomegaly, thrombocytopenia, anaemia, bleeding diathesis, liver failure and tubulopathy.
• European journal of pediatrics.Eur J Pediatr.2014 Feb 5. [Epub ahead of print]
• Transaldolase (TALDO) deficiency is a rare metabolic disease in the pentose phosphate pathway, which manifests as a severe, early-onset multisystem disease. The body fluids of affected patients contain increased polyol concentrations and seven-carbon chain carbohydrates. We report the molecular and
• PMID 24497183

Japanese Journal

• Metabolic changes during cataract formation by ultraviolet radiation in the incubated rabbit lens

• 北海道醫學雜誌 = Acta medica Hokkaidonensia 84(6), 423-430, 2009-11-01
• NAID 10029924774

• Nitric oxide attenuates cellular hexose monophosphate shunt response to oxidants in articular chondrocytes and acts to promote oxidant injury

• J. Cell. Physiol. 172, 183-191, 1997
• NAID 80009816685

• Methacrylonitrile-Induced Alterations in Carbohydrate Metabolism in the Rat.

• Journal of Clinical Biochemistry and Nutrition 22(1), 13-17, 1997
• NAID 130003670419

Related Links

• hexose-monophosphate shunt – Dictionary definition of ...

hexose-monophosphate shunt (pentose-phosphate shunt) A metabolic pathway, alternative to that of glycolysis, of carbohydrate interconversion: hexose-6-phosphate is converted into pentose-phosphate and carbon dioxide. The ...

• ホスホグルコン酸回路 - 福岡大学理学部化学科

ホスホグルコン酸回路は、ヘキソースリン酸側路(hexose monophosphate shunt, HMS) 、ペントースリン酸経路、Warburg-Dickens経路など、多くの別名で呼ばれる。 HMSは、解糖経路のグルコース-6-リン酸から枝分かれし HMSの 2 + ...

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★リンクテーブル★

リンク元	「ビタミンB1」「ペントースリン酸経路」「ヘキソースリン酸側路」「pentose shunt」「ヘキソース一リン酸シャント」
関連記事	「shunt」「monophosphate」「hexose」

「ビタミンB1」

　　[★]

英

vitamine B1

同

チアミン thiamine、塩酸チアミン thiamine hydrochloride、ビタミンB1塩酸塩、アノイリン aneurine

商

アミグランド、パレセーフ、ビーフリード

関

ビタミン、チアミン二リン酸 thiamine pyrophosphate チアミンピロリン酸 TPP

• 水溶性ビタミン

機能

• 補酵素

• 体内でリン酸化されてピロリン酸エステルであるチアミン二リン酸(TPP)となり機能する。
• α-ケト酸の酸化的脱炭酸反応(oxidative decarboxylation)、ケトール形成反応に関わる。
• 1. 解糖系からTCA回路を繋ぐ反応：チアミン二リン酸はピルビン酸デヒドロゲナーゼに非共有結合して、以下の脱炭酸反応を触媒

• ピルビン酸 + CoASH + NAD⁺　－(ピルビン酸デヒドロゲナーゼ)→　アセチルCoA + NADH + CO₂

• 2. TCA回路の反応

• α-ケトグルタル酸 + CoASH + NAD⁺ －(α-keto glutarate dehydrogenase)→　サクシニルCoA + NADH + CO₂

• 3. branched-chain ketoacid dehyrogenase: involved in metabolism of branched-chain amino acid; deficiency results in maple syrup urine disease

• 4. transketolase; hexose monophosphate shunt

• 5. 酵母などではアルコール発酵を行うピルビン酸デカルボキシラーゼ(ピルビン酸からCO₂を除去してアセトアルデヒドを産生)の補酵素として重要

• ピルビン酸－(ピルビン酸デカルボキシラーゼ)→アセトアルデヒド + CO₂

臨床関連

• ビタミンB₁欠乏症

• 脚気
• ウェルニッケ脳症、コルサコフ症候群

「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

「ヘキソースリン酸側路」

　　[★]

英

hexose monophosphate shunt

関

ペントース経路、ペントースリン酸経路

「pentose shunt」

　　[★]

• ペントース経路

関

hexose monophosphate shunt、pentose phosphate pathway

「ヘキソース一リン酸シャント」

　　[★]

英

[[]]

同

hexose monophosphate shunt

関

[[]]

同

hexose monophosphate shunt

「shunt」

　　[★]

• vt.

• ～をそらす

• n.

• 短絡、分路、(医療)吻合術、シャント、

→シャント

　 　 　 　 　 　

「monophosphate」

　　[★]

• n.

• 一リン酸塩、一リン酸エステル、一リン酸

「hexose」

　　[★]

• 六炭糖、ヘキソース