glutamate dehydrogenase

グルタミン酸脱水素酵素、グルタミン酸デヒドロゲナーゼ、GDH、GLDH

WordNet

1. a salt or ester of glutamic acid

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/07/12 16:40:52」(JST)

wiki en

[Wiki en表示]

glutamate dehydrogenase (GLDH)
Identifiers
EC number	1.4.1.2
CAS number	9001-46-1
Databases
IntEnz	IntEnz view
BRENDA	BRENDA entry
ExPASy	NiceZyme view
KEGG	KEGG entry
MetaCyc	metabolic pathway
PRIAM	profile
PDB structures	RCSB PDB PDBe PDBsum
Gene Ontology	AmiGO / EGO
Search PMC articles PubMed articles NCBI proteins

glutamate dehydrogenase [NAD(P)+]
Identifiers
EC number	1.4.1.3
CAS number	9029-12-3
Databases
IntEnz	IntEnz view
BRENDA	BRENDA entry
ExPASy	NiceZyme view
KEGG	KEGG entry
MetaCyc	metabolic pathway
PRIAM	profile
PDB structures	RCSB PDB PDBe PDBsum
Gene Ontology	AmiGO / EGO
Search PMC articles PubMed articles NCBI proteins

glutamate dehydrogenase (NADP+)
Identifiers
EC number	1.4.1.4
CAS number	9029-11-2
Databases
IntEnz	IntEnz view
BRENDA	BRENDA entry
ExPASy	NiceZyme view
KEGG	KEGG entry
MetaCyc	metabolic pathway
PRIAM	profile
PDB structures	RCSB PDB PDBe PDBsum
Gene Ontology	AmiGO / EGO
Search PMC articles PubMed articles NCBI proteins

Glutamate dehydrogenase (GLDH) is an enzyme, present in most microbes and the mitochondria of eukaryotes, as are some of the other enzymes required for urea synthesis, that converts glutamate to α-ketoglutarate, and vice versa. In animals, the produced ammonia is usually used as a substrate in the urea cycle. Typically, the α-ketoglutarate to glutamate reaction does not occur in mammals, as glutamate dehydrogenase equilibrium favours the production of ammonia and α-ketoglutarate. Glutamate dehydrogenase also has a very low affinity for ammonia (high Michaelis constant of about 1 mM), and therefore toxic levels of ammonia would have to be present in the body for the reverse reaction to proceed (that is, α-ketoglutarate and ammonia to glutamate and NAD(P)+). In bacteria, the ammonia is assimilated to amino acids via glutamate and aminotransferases. In plants, the enzyme can work in either direction depending on environment and stress. Transgenic plants expressing microbial GLDHs are improved in tolerance to herbicide, water deficit, and pathogen infections. They are more nutritionally valuable.

• Glutamate

• α-Ketoglutarate

The enzyme represents a key link between catabolic and metabolic pathways, and is, therefore, ubiquitous in eukaryotes.

Clinical application

GLDH can be measured in a medical laboratory to evaluate the liver function. Elevated blood serum GLDH levels indicate liver damage and GLDH plays an important role in the differential diagnosis of liver disease, especially in combination with aminotransferases. GLDH is localised in mitochondria, therefore practically none is liberated in generalised inflammatory diseases of the liver such as viral hepatitides. Liver diseases in which necrosis of hepatocytes is the predominant event, such as toxic liver damage or hypoxic liver disease, are characterised by high serum GLDH levels. GLDH is important for distinguishing between acute viral hepatitis and acute toxic liver necrosis or acute hypoxic liver disease, particularly in the case of liver damage with very high aminotransferases. In clinical trials, GLDH can serve as a measurement for the safety of a drug.

Cofactors

NAD⁺(or NADP⁺) is a cofactor for the glutamate dehydrogenase reaction, producing α-ketoglutarate and ammonium as a byproduct.

Based on which cofactor is used, glutamate dehydrogenase enzymes are divided into the following three classes:

• EC 1.4.1.2: L-glutamate + H₂O + NAD⁺ 2-oxoglutarate + NH₃ + NADH + H⁺
• EC 1.4.1.3: L-glutamate + H₂O + NAD(P)⁺ 2-oxoglutarate + NH₃ + NAD(P)H + H⁺
• EC 1.4.1.4: L-glutamate + H₂O + NADP⁺ 2-oxoglutarate + NH₃ + NADPH + H⁺

Role in flow of nitrogen

Ammonia incorporation in animals and microbes occurs through the actions of glutamate dehydrogenase and glutamine synthetase. Glutamate plays the central role in mammalian and microbe nitrogen flow, serving as both a nitrogen donor and a nitrogen acceptor.

Regulation of glutamate dehydrogenase

In humans, the activity of glutamate dehydrogenase is controlled through ADP-ribosylation, a covalent modification carried out by the gene sirt4. This regulation is relaxed in response to caloric restriction and low blood glucose. Under these circumstances, glutamate dehydrogenase activity is raised in order to increase the amount of α-ketoglutarate produced, which can be used to provide energy by being used in the citric acid cycle to ultimately produce ATP.

In microbes, the activity is controlled by the concentration of ammonium and or the like-sized rubidium ion, which binds to an allosteric site on GDH and changes the K_m (Michaelis constant) of the enzyme.

The control of GDH through ADP-ribosylation is particularly important in insulin-producing β cells. Beta cells secrete insulin in response to an increase in the ATP:ADP ratio, and, as amino acids are broken down by GDH into α-ketoglutarate, this ratio rises and more insulin is secreted. SIRT4 is necessary to regulate the metabolism of amino acids as a method of controlling insulin secretion and regulating blood glucose levels.

Bovine liver glutamate dehydrogenase was found to be regulated by nucleotides in the late 1950s and early 1960s by Carl Frieden. In addition to describing the effects of nucleotides like ADP, ATP and GTP he described in detail the different kinetic behavior of NADH and NADPH. As such it was one of the earliest enzymes to show what was later described as allosteric behavior.

Mutations alter the allosteric binding site of GTP cause permanent activation of glutamate dehydrogenase lead to disorder known as hyperinsulinism-hyperammonemia.

Regulation

Allosteric regulation:

This protein may use the morpheein model of allosteric regulation.

Allosteric inhibitors:

• Guanosine triphosphate (GTP)
• Guanosine diphosphate (GDP)
• Palmitoyl-CoA
• Zn²⁺

Activators:

• Adenosine diphosphate (ADP)
• Leucine
• l-isoleucine
• l-valine

Additionally, Mice GDH shows substrate inhibition by which GDH activity decreases at high glutamate concentrations.

Isozymes

Humans express the following glutamate dehydrogenase isozymes:

glutamate dehydrogenase 1 Identifiers Symbol GLUD1 Alt. symbols GLUD Entrez 2746 HUGO 4335 OMIM 138130 RefSeq NM_005271 UniProt P00367 Other data EC number 1.4.1.3 Locus Chr. 10 q21.1-24.3

glutamate dehydrogenase 2 Identifiers Symbol GLUD2 Alt. symbols GLUDP1 Entrez 2747 HUGO 4336 OMIM 300144 RefSeq NM_012084 UniProt P49448 Other data EC number 1.4.1.3 Locus Chr. X q25

See also

• Anaplerotic reactions

References

Amino acid sequence analysis of glutamate dehydrogenase from different source organisms==External links==

• Glutamate dehydrogenase at the US National Library of Medicine Medical Subject Headings (MeSH)

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

• 1. 成人におけるクロストリジウム・ディフィシル感染症：臨床症状および診断 clostridium difficile infection in adults clinical manifestations and diagnosis
• 2. 幼児の持続性高インスリン血症性低血糖症の病因、臨床的特徴、および診断 pathogenesis clinical features and diagnosis of persistent hyperinsulinemic hypoglycemia of infancy
• 3. 肝細胞障害を検出するための肝臓生化学検査 liver biochemical tests that detect injury to hepatocytes
• 4. 小児におけるクロストリジウムディフィシル感染：臨床的特徴および診断 clostridium difficile infection in children clinical features and diagnosis
• 5. 筋萎縮性側索硬化症の疫学および病因 epidemiology and pathogenesis of amyotrophic lateral sclerosis

English Journal

• Localization of SUCLA2 and SUCLG2 subunits of succinyl CoA ligase within the cerebral cortex suggests the absence of matrix substrate-level phosphorylation in glial cells of the human brain.

• Dobolyi A1, Bagó AG, Gál A, Molnár MJ, Palkovits M, Adam-Vizi V, Chinopoulos C.
• Journal of bioenergetics and biomembranes.J Bioenerg Biomembr.2015 Apr;47(1-2):33-41. doi: 10.1007/s10863-014-9586-4. Epub 2014 Nov 5.
• We have recently shown that the ATP-forming SUCLA2 subunit of succinyl-CoA ligase, an enzyme of the citric acid cycle, is exclusively expressed in neurons of the human cerebral cortex; GFAP- and S100-positive astroglial cells did not exhibit immunohistoreactivity or in situ hybridization reactivity
• PMID 25370487

• Ischemic tolerance in an in vivo model of glutamate preconditioning.

• Badawi Y1, Pal R, Hui D, Michaelis EK, Shi H.
• Journal of neuroscience research.J Neurosci Res.2015 Apr;93(4):623-32. doi: 10.1002/jnr.23517. Epub 2014 Nov 25.
• Ischemia initiates a complicated biochemical cascade of events that triggers neuronal death. This study focuses on glutamate-mediated neuronal tolerance to ischemia-reperfusion. We employed an animal model of lifelong excess release of glutamate, the glutamate dehydrogenase 1 transgenic (Tg) mouse,
• PMID 25421886

• Knockdown of STIM1 Improves Neuronal Survival After Traumatic Neuronal Injury Through Regulating mGluR1-Dependent Ca(2+) Signaling in Mouse Cortical Neurons.

• Hou PF1, Liu ZH, Li N, Cheng WJ, Guo SW.
• Cellular and molecular neurobiology.Cell Mol Neurobiol.2015 Mar;35(2):283-92. doi: 10.1007/s10571-014-0123-0. Epub 2014 Oct 11.
• Activation of glutamate receptors and followed increase of intracellular calcium concentration is a key pathological mechanism involved in secondary neuronal injury after traumatic brain injury (TBI). Stromal interaction molecule (STIM) proteins are considered to be important players in regulating n
• PMID 25304289

Japanese Journal

• Mutational analysis of ABCC8, KCNJ11, GLUD1, HNF4A and GCK genes in 30 Chinese patients with congenital hyperinsulinism

• Sang Yanmei,Xu Zidi,Liu Min,Yan Jie,Wu Yujun,Zhu Cheng,Ni Guichen
• Endocrine Journal 61(9), 901-910, 2014
• … All exons of the adenosine triphosphate (ATP)-sensitive potassium channel (KATP channel) genes KCNJ11 and ABCC8, the hepatocyte nuclear factor 4 α (HNF4A) gene, and the Glucokinase (GCK) gene as well as exons 6 and 7 and 10-12 of the glutamate dehydrogenase 1 (GLUD1) gene were amplified from genomic DNA and directly sequenced. … Glutamate dehydrogenase-CHI is the second most common cause of CHI, while HNF4A and GCK are rare types of CHI in Chinese patients. …
• NAID 130004690921

• Clostridium difficile感染症 (特集 医療関連感染症 : 起こさないためにどうするか? 起きてしまったらどうするか?) -- (医療関連感染症の主要な疾患)

• 大路 剛
• 内科 112(5), 921-924, 2013-11
• NAID 40019842566

• Resolving the Role of Plant Glutamate Dehydrogenase(2)Physiological Characterization of Plants Overexpressing the Two Enzyme Subunits Individually or Simultaneously

• Terce-Laforgue Therese,Bedu Magali,Dargel-Grafin Celine [他]
• Plant and cell physiology 54(10), 1635-1647, 2013-10
• NAID 40019838772

Related Links

• Glutamate dehydrogenaseとは - goo Wikipedia (ウィキペディア)

It has been suggested that Glutamate dehydrogenase 1 be merged into this article. (Discuss) Proposed since October 2011.

• Glutamate Dehydrogenase

Glutamate dehydrogenase (GDH) is located in the mitochondria and is an important branch-point enzyme between carbon and nitrogen metabolism (13). GDH catalyzes the reversible NAD (P) +-linked oxidative deamination of L-glutamate into alpha ketoglutarate and ammonia in two steps.

Related Pictures

---

★リンクテーブル★

リンク元	「グルタミン酸脱水素酵素」「GDH」「GLDH」
拡張検索	「NADPH-dependent glutamate dehydrogenase」「glutamate dehydrogenase遺伝子異常」「glutamate dehydrogenase gene mutation」
関連記事	「glutamate」「dehydrogenase」「dehydrogenases」

「グルタミン酸脱水素酵素」

　　[★]

英

glutamate dehydrogenase, GLDH, GDH

同

グルタミン酸デヒドロゲナーゼ

[show details]

グルタミン酸脱水素酵素 : 約 59,600 件
グルタミン酸デヒドロゲナーゼ : 約 5,220 件

グルタミン酸脱水素酵素 GDH : 87 件
グルタミン酸デヒドロゲナーゼ GDH : 約 86 件

「GDH」

　　[★]

• グルコース脱水素酵素 グルコースデヒドロゲナーゼ glucose dehydrogenase
• グルタミン酸脱水素酵素 グルタミン酸デヒドロゲナーゼ glutamate dehydrogenase

「GLDH」

　　[★] グルタミン酸脱水素酵素、グルタミン酸デヒドロゲナーゼ、glutamate dehydrogenase、GDH

「NADPH-dependent glutamate dehydrogenase」

　　[★]

NADPH依存性グルタミン酸脱水素酵素、NADPH依存性グルタミン酸デヒドロゲナーゼ

「glutamate dehydrogenase遺伝子異常」

　　[★]

英

glutamate dehydrogenase gene mutation

関

グルタミン酸脱水素酵素

「glutamate dehydrogenase gene mutation」

　　[★] glutamate dehydrogenase遺伝子異常

「glutamate」

　　[★]

グルタミン酸、グルタメート、グルタメイト、(化合物)グルタミン酸塩

　

「dehydrogenase」

　　[★] 脱水素酵素 デヒドロゲナーゼ

「dehydrogenases」

　　[★] 脱水素酵素 デヒドロゲナーゼ