Warburg-Dickens pathway

ワールブルグ・ディケンズ経路

WordNet

1. German art historian (1866-1929) (同)Aby Warburg, Aby Moritz Warburg
2. German biochemist who pioneered the use of chemical techniques in biological investigations; noted for studies of cellular respiration (1883-1970) (同)Otto Heinrich Warburg
3. English writer whose novels depicted and criticized social injustice (1812-1870) (同)Charles Dickens, Charles John Huffam Dickens
4. a trodden path (同)footpath

PrepTutorEJDIC

1. ディケンズ(『Charles ~』;1812‐70;英国の小説家)
2. 道,小道(path)
3. 悪魔

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/02/07 21:42:59」(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 biochemical pathway parallel to glycolysis that generates NADPH and pentoses (5-carbon sugars). 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.

Similar to glycolysis, the pentose phosphate pathway appears to have a very ancient evolutionary origin. The reactions of this pathway are (mostly) enzyme catalysed in modern cells. They also occur however non-enzymatically under conditions that replicate those of the Archean ocean, and are then catalyzed by metal ions, ferrous iron Fe(II) in particular. The origins of the pathway could thus 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.

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 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⁺. 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.

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.

See also

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

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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English Journal

• Energy metabolism in Capnocytophaga ochracea.

• Calmes R, Rambicure GW, Gorman W, Lillich TT.
• Infection and immunity.Infect Immun.1980 Aug;29(2):551-60.
• Among the microflora of the gingival sulcus are members of the genus Capnocytophaga which have been implicated as possible etiological agents of juvenile periodontitis and systemic infectious diseases. In this study, the pathway used by C. ochracea strain 25 for generating energy from glucose was in
• PMID 7216425

• Histochemical studies on the distribution of some enzymes concerned with carbohydrate metabolism in the locus ceruleus, nucleus tractus mesencephalicus n. trigemini, nucleus dorsalis n. vagi and nucleus n. hypoglossi of the rat.

• Iijima K, Imai K.
• Acta histochemica.Acta Histochem.1975;52(1):145-63.
• Detailed histochemical studies have been conducted on the distribution of hexokinase, amylophosphorylase, aldolase, lactic dehydrogenase, succinic dehydrogenase and glucose-6-phosphate dehydrogenase in every component of the locus ceruleus, nucleus tractus mesencephalicus n. trigemini, nucleus dorsa
• PMID 809976

• [Studies on the metabolic activity of the Warburg-Dickens pathway in the red blood cell].

• Misaki C.
• Nihon Naika Gakkai zasshi. The Journal of the Japanese Society of Internal Medicine.Nihon Naika Gakkai Zasshi.1965 Dec 10;54(9):1045-59.
• PMID 5894571

Japanese Journal

• 高血圧性脳内出血の外科的治療に関する実験的研究--組織化学的研究

• 本条 征史
• 岡山医学会雑誌 88(9・10), p889-911, 1976-10
• … In the non-medicated group, enzymatic activities of LDH of Embden-Meyerhof pathway, SDH and MDH of TCA cycle, Cy-O of the electron transport system and also Al-p, Ac-p of the hydrolytic enzymes were diminished in the adjacent area of the hematoma. … In contrast, G-6-PDH of Warburg-Dickens pathway was accelerated in the cortex. …
• NAID 120002353698

• Studies on the abnormalities of glucuronic acid pathway in diabetes mellitus:(1) Changes of metabolic factors in glucuronidation and hydrolysis of glucuronides in alloxan diabetic rats

• 野口 英機,鬼原 彰,島田 孝,石井 禎郎,大原 弘通
• 糖尿病 13(2), 211-217, 1970
• … As to the abnormalities of carbohydrate metabolism in diabetes mellitus, manifest depression in Embden-Myerhof cycle and Warburg Dickens pathway was pointed out. … A.) pathway in diabetes mellitus, especially in relation to abnormalities of mucopolysaccharide metabolism.<BR>In order to make the above remarks clear, several metabolic factors: in G. … pathway were studied in alloxan diabetic (A. … pathway. …
• NAID 130004114641

• 実験的脳出血の組織学的および組織化学的研究

• 佐藤 宏二
• 岡山医学会雑誌 80(9・10), 881-903, 1968-10
• … However, in general the activity of phosphorylase of the glycogen cycle, lactic dehydrogenase of Embden-Meyerhof pathway, glucose-6-phosphate dehydrogenase of Warburg-Dickens cycle, and DPN-diaphorase activity of the ion transport system were accelerated. …
• NAID 120002398191

Related Links

• Warburg-Dickens pathway | Online references | cyclopaedia.net

References for "Warburg-Dickens pathway" im Internet, an Universitäten und in der Literatur... cyclopaedia.net ... The emergence of “cancer energy metabolism” as one of the promising targets, is affirmed by the two significant ...

• Warburg-Dickens-Horecker shunt - definition of Warburg ...

pathway /path·way/ (path´wa) 1. a course usually followed. 2. the nerve structures through which an impulse passes between groups of nerve cells or between the central nervous system and an organ or muscle. 3. metabolic p.. ...

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

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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

「Warburg」

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ワールブルグ、ワールブルク 　 　

「pathway」

　　[★]

• 経路、パスウェイ

関

route