Glutamate dehydrogenase
| Glutamate dehydrogenase (NADP +) 1 | ||
|---|---|---|
| Mass / length primary structure | 505 amino acids | |
| Secondary to quaternary structure | Homohexamer | |
| Identifier | ||
| Gene name (s) | GLUD1 , GLUD2 | |
| External IDs | ||
| Enzyme classification | ||
| EC, category | 1.4.1.3 , oxidoreductase | |
| Substrate | L -glutamate + H 2 O + NAD + | |
| Products | 2-oxoglutarate + NH 3 + NADH / H + | |
Glutamate dehydrogenase (GDH, also GLDH) is the name of the enzyme that catalyzes the reaction of L - glutamate , water and NAD (P) + to form ammonium , α-ketoglutarate (2-oxoglutarate) and NAD (P) H or their reverse reaction . It is thus part of nitrogen metabolism and of central importance for the fixation ( assimilation ) or release ( dissimilation ) of ammonium. GDH is found in many organisms . In humans, there are two genes ( GLUD1 and GLUD2 ) that code for two isoforms of GDH, with GLUD2 being particularly expressed in the retina , testes and also in the brain. Mutations in GLUD1 can lead to hyperinsulinism - hyperammonaemia syndrome.
While the GDHs of higher eukaryotes can use both co-factors ( NADH and NADPH ), the GDHs of prokaryotes and lower eukaryotes are dependent on a certain coenzyme (NADH or NADPH, EC 1.4.1.2 and EC 1.4.1.4 ). Here, NADPH-dependent GDHs are usually anabolic enzymes and catalyze the assimilation of ammonium, while NADH-dependent GDHs contribute to catabolism and mostly dissimilate ammonium.
Occurrence
The GDH occurs exclusively in mitochondria, which plays a role in the diagnosis of liver damage. Unlike aspartate aminotransferase (ASAT) or alanine aminotransferase (ALAT), it only enters the blood when liver cells have been completely destroyed.
Catalyzed reaction
The catalyzed reaction of GDH with L -glutamate ( 1 ) is shown in the scheme below. This is deaminated and oxidized by the enzyme to α-ketoglutarate ( 2 ) . The released ammonium (NH 4 + ) can get into the urea cycle for further dissimilation .
construction
All GDHs examined so far are homomeric enzyme complexes, which are built up from either six or four identical subunits. These subunits are either 50 kDa , 115 kDa or 180 kDa in size. GDHs are divided into four classes according to the number and size of the subunits and on the basis of sequence comparisons: α6-50I and α6-50II (small GDHs) and α4-115 and α6-180 (large GDHs). The GDHs of all four classes are based on the same catalytic mechanism, they have a very similar domain structure and numerous highly conserved amino acid residues . So far nothing is known about the function of the additional amino acids of the large GDHs (α4-115 and α6-180).
The GDH from Clostridium symbiosum is one of the best investigated GDHs to date. It is NADH-dependent and belongs to the α6-50I class. Each of the six identical subunits of this enzyme complex consists of two domains, which are separated by a column, the active center . One of the two domains has the binding site for NADH, while the other domain binds L- glutamate or α-ketoglutarate. During the catalytic cycle the gap closes and the substrates are thereby brought into a position favorable for the reaction.
