Glutamate dehydrogenase

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{{STRUCTURE_1gtm| PDB=1gtm | SIZE=400| SCENE= |right|CAPTION=Glutamate dehydrogenase trimer complex with sulfate, [[1gtm]] }}
{{STRUCTURE_1gtm| PDB=1gtm | SIZE=400| SCENE= |right|CAPTION=Glutamate dehydrogenase trimer complex with sulfate, [[1gtm]] }}
== Function ==
== Function ==
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'''Glutamate dehydrogenase''' (GLDH) catalyzes the reversible conversion of glutamate to α-ketoglutarate and ammonium. The ammonia is removed via the urea cycle. [[NAD]] or NADP is a cofactor in GLDH activity. NAD is a cofactor in the forward reaction while NADP is a cofactor in the reverse reaction. GLDH is regulated by the cell’s energy state. ATP and GTP inhibit the enzyme while ADP, GDP and leucine positively enhance it<ref>PMID:14299621</ref>. '''Glutamate dehydrogenase 1''' (GLDH1) catalyzes the deamination of glutamate to 2-oxoglutarate and ammonium. GLDH1 is regulated in the same manner as GLDH.
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'''Glutamate dehydrogenase''' (GLDH) catalyzes the reversible conversion of glutamate to α-ketoglutarate and ammonium. The ammonia is removed via the urea cycle. [[NAD]] or NADP is a cofactor in GLDH activity. NAD is a cofactor in the forward reaction while NADP is a cofactor in the reverse reaction. GLDH is regulated by the cell’s energy state. ATP and GTP inhibit the enzyme while ADP, GDP and leucine positively enhance it<ref>PMID:14299621</ref>. '''Glutamate dehydrogenase 1''' (GLDH1) catalyzes the deamination of glutamate to 2-oxoglutarate and ammonium. GLDH1 is regulated in the same manner as GLDH<ref>PMID:12054821</ref>.
== Relevance ==
== Relevance ==
Elevated GLDH values in blood serum indicate liver malfunction.
Elevated GLDH values in blood serum indicate liver malfunction.
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== Disease ==
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Mutations in GLDH1 are associated with familial hyperinsulinism<ref>PMID:10453735</ref>.
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== Structural highlights ==
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The glutamate binding pocket of GLDH is in a cleft between the two domains of the enzyme with residue D165 serving as a general base and a protein-bound water molecule as the attacking nucleophile <ref>PMID:8263917</ref>.
==3D structures of glutamate dehydrogenase==
==3D structures of glutamate dehydrogenase==

Revision as of 11:12, 8 March 2016

Template:STRUCTURE 1gtm

Contents

Function

Glutamate dehydrogenase (GLDH) catalyzes the reversible conversion of glutamate to α-ketoglutarate and ammonium. The ammonia is removed via the urea cycle. NAD or NADP is a cofactor in GLDH activity. NAD is a cofactor in the forward reaction while NADP is a cofactor in the reverse reaction. GLDH is regulated by the cell’s energy state. ATP and GTP inhibit the enzyme while ADP, GDP and leucine positively enhance it[1]. Glutamate dehydrogenase 1 (GLDH1) catalyzes the deamination of glutamate to 2-oxoglutarate and ammonium. GLDH1 is regulated in the same manner as GLDH[2].

Relevance

Elevated GLDH values in blood serum indicate liver malfunction.

Disease

Mutations in GLDH1 are associated with familial hyperinsulinism[3].

Structural highlights

The glutamate binding pocket of GLDH is in a cleft between the two domains of the enzyme with residue D165 serving as a general base and a protein-bound water molecule as the attacking nucleophile [4].

3D structures of glutamate dehydrogenase

Updated on 08-March-2016

References

  1. ↑ FRIEDEN C. GLUTAMATE DEHYDROGENASE. VI. SURVEY OF PURINE NUCLEOTIDE AND OTHER EFFECTS ON THE ENZYME FROM VARIOUS SOURCES. J Biol Chem. 1965 May;240:2028-35. PMID:14299621
  2. ↑ Smith TJ, Schmidt T, Fang J, Wu J, Siuzdak G, Stanley CA. The structure of apo human glutamate dehydrogenase details subunit communication and allostery. J Mol Biol. 2002 May 3;318(3):765-77. PMID:12054821 doi:10.1016/S0022-2836(02)00161-4
  3. ↑ Yorifuji T, Muroi J, Uematsu A, Hiramatsu H, Momoi T. Hyperinsulinism-hyperammonemia syndrome caused by mutant glutamate dehydrogenase accompanied by novel enzyme kinetics. Hum Genet. 1999 Jun;104(6):476-9. PMID:10453735
  4. ↑ Stillman TJ, Baker PJ, Britton KL, Rice DW. Conformational flexibility in glutamate dehydrogenase. Role of water in substrate recognition and catalysis. J Mol Biol. 1993 Dec 20;234(4):1131-9. PMID:8263917 doi:http://dx.doi.org/10.1006/jmbi.1993.1665

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Michal Harel, Alexander Berchansky, Joel L. Sussman

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