Glutamate dehydrogenase

• OMIM: 138130
• UniProt: P04035

Glutamate dehydrogenase (GDH, and GLDH ) is the enzyme that catalyzes the reaction of L-glutamate, water and NAD (P) to ammonia, α -ketoglutarate and NAD (P) H or its reverse reaction. Thus it is a part of the nitrogen metabolism and for the fixation ( assimilation ) or release ( dissimilation ) of ammonium is of central importance. GDH is present in many organisms. In humans, there are two genes ( GLUD1 and GLUD2 ) encoding two isoforms of GDH, which is expressed GLUD2 particularly in the retina, the testes and the brain. Mutations at GLUD1 can lead to hyperinsulinism - hyperammonemia syndrome.

While the GDHs higher eukaryotes can use both cofactors (NADH and NADPH ) are GDHs of prokaryotes and lower eukaryotes of a specific coenzyme -dependent ( NADH or NADPH, EC 1.4.1.2 and EC 1.4.1.4 ). This NADPH-dependent GDHs are usually anabolic enzymes and catalyze the assimilation of ammonium, while NADH - dependent GDHs contribute to catabolism and ammonium usually dissimilieren.

Occurrence

The GDH is found only in mitochondria, in the diagnosis of liver damage plays a role. You reached namely unlike aspartate aminotransferase ( AST ) or alanine aminotransferase ( ALAT ) getting into the blood when liver cells are completely destroyed.

Catalyzed reaction

The catalyzed reaction of the GDH with L-glutamate (1) is shown in the scheme below. This is deaminated and oxidized (2 ) by the enzyme α -ketoglutarate. The liberated ammonium (NH4 ) can go to the other dissimilation in the urea cycle.

Construction

In all previously examined GDHs is homomeric Enyzmkomplexe, which are composed of either four or six identical subunits. These subunits are either 50 kDa, 115 kDa or 180 kDa in size. GDHs be classified according to the number and size of subunits and on the basis of sequence comparisons into four classes: α6 - α6 - 50I and 50II (small GDHs ) and α4 -115 and α6 -180 (large GDHs ). The GDHs all four classes is the same catalytic mechanism to reason, they have a very similar domain structure and numerous highly conserved amino acid residues. The function of the additional amino acids of the large GDHs ( α4 - α6 - 115 and 180) is so far not known.

The GDH from Clostridium symbiosum is one of the most thoroughly studied GDHs. It is NADH - dependent and is part of the α6 - 50I class. Each of six identical subunits of this enzyme complex consists of two domains, which are separated by a column, the active site. One of the two domains has the Bindstelle of NADH, while the other domain, L-glutamate or α -ketoglutarate binds. During the catalytic cycle, the gap closes and the substrates are thereby brought into a favorable position for the reaction.