関: alpha-ketoglutarate

WordNet

first in order of importance; "the alpha male in the group of chimpanzees"; "the alpha star in a constellation is the brightest or main star"
the 1st letter of the Greek alphabet
the beginning of a series or sequence; "the Alpha and Omega, the first and the last, the beginning and the end"--Revelations
early testing stage of a software or hardware product; "alpha version"
street name for lysergic acid diethylamide (同)back breaker, battery-acid, dose, dot, Elvis, loony toons, Lucy in the sky with diamonds, pane, superman, window pane, Zen
any of various water-soluble compounds having a sour taste and capable of turning litmus red and reacting with a base to form a salt
having the characteristics of an acid; "an acid reaction"
any high mountain

PrepTutorEJDIC

アルファ(ギリシア語アルファベットの第1字A,α;英語のA,aに相当) / アルファ星(星座の主星)
酸性の / 酸味のある,すっぱい(sour) / (言葉・態度などが)厳しい,しんらつな / 酸 / すっぱいもの / 《俗》=LSD
高山,高峰

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2017/05/27 03:02:27」(JST)

wiki en

α-Ketoglutaric acid is one of two ketone derivatives of glutaric acid. (The term "ketoglutaric acid," when not further qualified, almost always refers to the alpha variant. β-Ketoglutaric acid varies only by the position of the ketone functional group, and is much less common.)

Its anion, α-ketoglutarate (α-KG, also called oxo-glutarate) is an important biological compound. It is the keto acid produced by deamination of glutamate, and is an intermediate in the Krebs cycle.

Functions

Alanine transaminase

The alanine transaminase (ALT) enzyme converts α-Ketoglutarate and L-alanine to L-glutamate and pyruvate, respectively, as a reversible process.

Krebs cycle

α-Ketoglutarate is a key intermediate in the Krebs cycle, coming after isocitrate and before succinyl CoA. Anaplerotic reactions can replenish the cycle at this juncture by synthesizing α-ketoglutarate from transamination of glutamate, or through action of glutamate dehydrogenase on glutamate.

Formation of amino acids

Glutamine is synthesized from glutamate by glutamine synthetase, which utilizes an ATP to form glutamyl phosphate; this intermediate is attacked by ammonia as a nucleophile giving glutamine and inorganic phosphate.

Nitrogen transporter

Another function is to combine with nitrogen released in the cell, therefore preventing nitrogen overload.

α-Ketoglutarate is one of the most important nitrogen transporters in metabolic pathways. The amino groups of amino acids are attached to it (by transamination) and carried to the liver where the urea cycle takes place.

α-Ketoglutarate is transaminated, along with glutamine, to form the excitatory neurotransmitter glutamate. Glutamate can then be decarboxylated (requiring vitamin B₆) into the inhibitory neurotransmitter GABA.

It is reported that high ammonia and/or high nitrogen levels may occur with high protein intake, excessive aluminum exposure, Reye's syndrome, cirrhosis, and urea cycle disorder.

It plays a role in detoxification of ammonia in brain.^[2]^[3]^[4]

Relationship to molecular oxygen

Acting as a co-substrate, it also plays important function in oxidation reactions involving molecular oxygen.

Molecular oxygen (O₂) directly oxidizes many compounds to produce useful products in an organism, such as antibiotics, etc., in reactions catalyzed by oxygenases. In many oxygenases, α-ketoglutarate helps the reaction by being oxidized together with the main substrate. In fact, one of the α-ketoglutarate-dependent oxygenases is an O₂ sensor, informing the organism the oxygen level in its environment.

In combination with molecular oxygen, alpha-ketoglutarate is one of the requirements for the hydroxylation of proline to hydroxyproline in the production of Type 1 Collagen.

Antioxidant

α-Ketoglutarate, which is known to be released by several cell types, decreased the levels of hydrogen peroxide, and the α-ketoglutarate was depleted and converted to succinate in cell culture media.^[5]

Longevity

A study released on May 14, 2014 links α-ketoglutarate with significantly increased lifespan in nematode worms. ^[6]

Immune regulation

A recent study has shown that α-ketoglutarate promotes TH1 differentiation and depletion of glutamine (by depleting its metabolite, α-ketoglutarate favors treg (regulatory T-cell) differentiation. It might play a role in skewing the balance in favor of tregs in the setting of the amino acid deprivation that can be seen in the tumor microenvironment.^[7]

Production

α-Ketoglutarate can be produced by:

Oxidative decarboxylation of isocitrate by isocitrate dehydrogenase;
Oxidative deamination of glutamate by glutamate dehydrogenase.
From Galacturonic acid by the organism agrobacterium tumefaciens.^[8]

Alpha-ketoglutarate can be used to produce:

Creatine-alpha ketoglutarate

Interactive pathway map

Click on genes, proteins and metabolites below to link to respective articles. ^{[§ 1]}

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|{{{bSize}}}px|alt=TCA Cycle edit]]

File:TCACycle WP78.png

TCA Cycle edit

^ The interactive pathway map can be edited at WikiPathways: "TCACycle_WP78".

References

^ Merck Index, 13th Edition, 5320.
^ Does infectious fever relieve autistic behavior by releasing glutamine from skeletal muscles as provisional fuel?
^ Ott, P; Clemmesen, O; Larsen, FS (Jul 2005). "Cerebral metabolic disturbances in the brain during acute liver failure: from hyperammonemia to energy failure and proteolysis.". Neurochemistry international. 47 (1–2): 13–8. doi:10.1016/j.neuint.2005.04.002. PMID 15921824.
^ Hares, P; James, IM; Pearson, RM (May–Jun 1978). "Effect of ornithine alpha ketoglutarate (OAKG) on the response of brain metabolism to hypoxia in the dog." (PDF). Stroke; a journal of cerebral circulation. 9 (3): 222–4. doi:10.1161/01.STR.9.3.222. PMID 644619.
^ Long, L; Halliwell, B (2011). "Artefacts in cell culture: α-Ketoglutarate can scavenge hydrogen peroxide generated by ascorbate and epigallocatechin gallate in cell culture media.". Biochemical and Biophysical Research Communications. 406 (1): 20–24. doi:10.1016/j.bbrc.2011.01.091. PMID 21281600.
^ Chin, RM; Fu, X; Pai, MY; Vergnes, L; Hwang, H; Deng, G; Diep, S; Lomenick, B; Meli, VS; Monsalve, GC; Hu, E; Whelan, SA; Wang, JX; Jung, G; Solis, GM; Fazlollahi, F; Kaweeteerawat, C; Quach, A; Nili, M; Krall, AS; Godwin, HA; Chang, HR; Faull, KF; Guo, F; Jiang, M; Trauger, SA; Saghatelian, A; Braas, D; Christofk, HR; Clarke, CF; Teitell, MA; Petrascheck, M; Reue, K; Jung, ME; Frand, AR; Huang, J (2014). "The metabolite α-ketoglutarate extends lifespan by inhibiting ATP synthase and TOR". Nature. 510: 397–401. doi:10.1038/nature13264. PMC 4263271 . PMID 24828042.
^ Klysz, Dorota; Tai, Xuguang (29 Sep 2015). "Glutamine-dependent α-ketoglutarate production regulates the balance between T helper 1 cell and regulatory T cell generation". Science Signaling. American Association for the Advancement of Science. 8 (396): ra97. doi:10.1126/scisignal.aab2610. Retrieved 14 October 2015.
^ Richard, Peter; Hilditch, Satu (2009). "d-Galacturonic acid catabolism in microorganisms and its biotechnological relevance". Applied Microbiology and Biotechnology. 82 (4): 597–604. doi:10.1007/s00253-009-1870-6. ISSN 0175-7598. PMID 19159926.

UpToDate Contents

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English Journal

Direct Analysis of Free and Sulfite-Bound Carbonyl Compounds in Wine by Two-Dimensional Quantitative Proton and Carbon Nuclear Magnetic Resonance Spectroscopy.

Nikolantonaki M1, Magiatis P2, Waterhouse AL1.
Analytical chemistry.Anal Chem.2015 Nov 3;87(21):10799-806. doi: 10.1021/acs.analchem.5b01682. Epub 2015 Oct 23.
Recent developments that have accelerated 2D NMR methods and improved quantitation have made these methods accessible analytical procedures, and the large signal dispersion allows for the analysis of complex samples. Few natural samples are as complex as wine, so the application to challenges in win
PMID 26348554

Metabolic engineering in the biotechnological production of organic acids in the tricarboxylic acid cycle of microorganisms: Advances and prospects.

Yin X1, Li J2, Shin HD3, Du G2, Liu L4, Chen J5.
Biotechnology advances.Biotechnol Adv.2015 Nov 1;33(6 Pt 1):830-41. doi: 10.1016/j.biotechadv.2015.04.006. Epub 2015 Apr 19.
Organic acids, which are chemically synthesized, are also natural intermediates in the metabolic pathways of microorganisms, among which the tricarboxylic acid (TCA) cycle is the most crucial route existing in almost all living organisms. Organic acids in the TCA cycle include citric acid, α-ketogl
PMID 25902192

Identification of Two Aliphatic Position Isomers between α- and β-Ketoglutaric Acid by Using a Briggs-Rauscher Oscillating System.

Zhang Y1, Hu G1, Hu L2, Song J1.
Analytical chemistry.Anal Chem.2015 Oct 6;87(19):10040-6. doi: 10.1021/acs.analchem.5b02649. Epub 2015 Sep 9.
This paper reports a novel method for identification of two aliphatic position isomers between α-ketoglutaric acid (α-KA) and β-ketoglutaric acid (β-KA) by their different perturbation effects on a Briggs-Rauscher oscillating system, in which tetraaza-macrocyclic complex [NiL](ClO4)2 is used as
PMID 26322368

Japanese Journal

Simultaneous Quantitation of Alpha-ketoglutaric Acid and 5-Hydroxymethylfurfural in Plasma by HPLC with UV and Fluorescence Detection

DONNARUMMA Fabrizio,WINTERSTEIGER Reinhold,SCHOBER Margot [他]
Analytical Sciences 29(12), 1177-1182, 2013-12
NAID 40019904897

Simultaneous Quantitation of Alpha-ketoglutaric Acid and 5-Hydroxymethylfurfural in Plasma by HPLC with UV and Fluorescence Detection

, , , , , , ,
Analytical Sciences 29(12), 1177-1182, 2013
… Alpha-ketoglutaric acid (KG) and hydroxymethylfurfural (HMF) are currently being investigated in clinical trials as an approach in targeted cancer therapy. … The derivatization step is based on the reaction of the carbonyl groups of KG and HMF with dansylhydrazine (DNSH) catalyzed by trifluoroacetic acid. …
NAID 130004827324

Multimethod Characterization of the Interaction of Aluminum Ion with .ALPHA.-Ketoglutaric Acid in Acidic Aqueous Solutions.

, , , ,
Analytical Sciences 19(2), 273-279, 2003
It has recently been reported that aluminum plays a very important role in reducing the activity of Krebs-cycle enzymes and glutamate dehydrogenase in rat brain homogenate. Therefore, it is necessary …
NAID 130004440710

Related Pictures

★リンクテーブル★

リンク元	「αケトグルタール酸」「α-ケトグルタール酸」「alpha-ketoglutarate」
関連記事	「ketoglutaric acid」「alpha」

「αケトグルタール酸」

α-Ketoglutaric acid^[1]
Names
	IUPAC name 2-Oxopentanedioic acid
	Other names 2-Ketoglutaric acid; alpha-Ketoglutaric acid; 2-Oxoglutaric acid; Oxoglutaric acid
Identifiers
CAS Number	328-50-7 ;
3D model (Jmol)	Interactive image;
ChEBI	CHEBI:30915 ;
ChemSpider	50 ;
DrugBank	DB02926 ;
ECHA InfoCard	100.005.756
IUPHAR/BPS	3636;
KEGG	C00026 ;
MeSH	alpha-ketoglutaric+acid
PubChem CID	51;
UNII	8ID597Z82X ;
	InChI InChI=1S/C5H6O5/c6-3(5(9)10)1-2-4(7)8/h1-2H2,(H,7,8)(H,9,10) Key: KPGXRSRHYNQIFN-UHFFFAOYSA-N ; InChI=1/C5H6O5/c6-3(5(9)10)1-2-4(7)8/h1-2H2,(H,7,8)(H,9,10) Key: KPGXRSRHYNQIFN-UHFFFAOYAN ;
	SMILES O=C(O)C(=O)CCC(=O)O ;
Properties
Chemical formula	C5H6O5
Molar mass	146.11 g/mol
Melting point	115 °C (239 °F; 388 K)
	Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
	verify (what is ?)
	Infobox references

　　[★]

英: alpha-ketoglutaric acid
関: α-ケトグルタール酸、α-ケトグルタル酸、αケトグルタル酸

「α-ケトグルタール酸」

　　[★]

英: alpha-ketoglutaric acid
関: αケトグルタール酸、α-ケトグルタル酸、αケトグルタル酸

「alpha-ketoglutarate」

　　[★]

αケトグルタル酸

関: alpha-ketoglutaric acid

alpha-ketoglutaric acid

「ketoglutaric acid」

　　[★]

ケトグルタル酸、ケトグルタール酸

関: ketoglutarate、oxoglutarate

「alpha」

　　[★]

α、アルファ

関: alfa

[WikiPathways-9] The interactive pathway map can be edited at WikiPathways: "TCACycle_WP78".

[1] Merck Index, 13th Edition, 5320.

[2] Does infectious fever relieve autistic behavior by releasing glutamine from skeletal muscles as provisional fuel?

[3] Ott, P; Clemmesen, O; Larsen, FS (Jul 2005). "Cerebral metabolic disturbances in the brain during acute liver failure: from hyperammonemia to energy failure and proteolysis.". Neurochemistry international. 47 (1–2): 13–8. doi:10.1016/j.neuint.2005.04.002. PMID 15921824.

[4] Hares, P; James, IM; Pearson, RM (May–Jun 1978). "Effect of ornithine alpha ketoglutarate (OAKG) on the response of brain metabolism to hypoxia in the dog." (PDF). Stroke; a journal of cerebral circulation. 9 (3): 222–4. doi:10.1161/01.STR.9.3.222. PMID 644619.

[5] Long, L; Halliwell, B (2011). "Artefacts in cell culture: α-Ketoglutarate can scavenge hydrogen peroxide generated by ascorbate and epigallocatechin gallate in cell culture media.". Biochemical and Biophysical Research Communications. 406 (1): 20–24. doi:10.1016/j.bbrc.2011.01.091. PMID 21281600.

[doi:10.1038.2Fnature13264-6] Chin, RM; Fu, X; Pai, MY; Vergnes, L; Hwang, H; Deng, G; Diep, S; Lomenick, B; Meli, VS; Monsalve, GC; Hu, E; Whelan, SA; Wang, JX; Jung, G; Solis, GM; Fazlollahi, F; Kaweeteerawat, C; Quach, A; Nili, M; Krall, AS; Godwin, HA; Chang, HR; Faull, KF; Guo, F; Jiang, M; Trauger, SA; Saghatelian, A; Braas, D; Christofk, HR; Clarke, CF; Teitell, MA; Petrascheck, M; Reue, K; Jung, ME; Frand, AR; Huang, J (2014). "The metabolite α-ketoglutarate extends lifespan by inhibiting ATP synthase and TOR". Nature. 510: 397–401. doi:10.1038/nature13264. PMC 4263271 . PMID 24828042.

[DOI:10.1126.2Fscisignal.aab2610-7] Klysz, Dorota; Tai, Xuguang (29 Sep 2015). "Glutamine-dependent α-ketoglutarate production regulates the balance between T helper 1 cell and regulatory T cell generation". Science Signaling. American Association for the Advancement of Science. 8 (396): ra97. doi:10.1126/scisignal.aab2610. Retrieved 14 October 2015.

[RichardHilditch2009-8] Richard, Peter; Hilditch, Satu (2009). "d-Galacturonic acid catabolism in microorganisms and its biotechnological relevance". Applied Microbiology and Biotechnology. 82 (4): 597–604. doi:10.1007/s00253-009-1870-6. ISSN 0175-7598. PMID 19159926.

v t e Citric acid cycle metabolic pathway
			Oxaloacetate			Malate			Fumarate			Succinate			Succinyl-CoA


Acetyl-CoA				NADH + H⁺	NAD⁺			H₂O		FADH₂	FAD		CoA + ATP(GTP)	P_i + ADP(GDP)
	+	H₂O														NADH + H⁺ + CO₂
		CoA														NAD⁺
					H₂O		H₂O			NAD(P)⁺	NAD(P)H + H⁺			CO₂


			Citrate			cis-Aconitate			Isocitrate			Oxalosuccinate			α-Ketoglutarate

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案内

案内

alpha-ketoglutaric acid