Glutamate Dehydrogenase
Glutamate / Glutamine

DEFINITION

Glutamate dehydrogenase 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.

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+ = 2-oxoglutarate + NH3 + NADH + H+
EC 1.4.1.4 L-glutamate + H2O + NADP+ = 2-oxoglutarate + NH3 + NADPH + H+

Humans express the following glutamate dehydrogenase isozymes:

glutamate dehydrogenase 1 and glutamate dehydrogenase 2

GLUD1 encodes glutamate dehydrogenase protein, a mitochondrial matrix enzyme that catalyzes the oxidative deamination of glutamate to alpha-ketoglutarate and ammonia.

Glutamate dehydrogenase 2, mitochondrial
Glutamate dehydrogenase 1, mitochondrial

THE GENE

Protein Aminoacids Percentage (Width 700 px)

SYNTHESIS AND TURNOVER

mRNA synthesis
protein synthesis

post-translational modifications

ADP-ribosylation

Reanalysis of phosphoproteomics data uncovers ADP-ribosylation sites 2012

A recent editorial in Nature Methods1 stated that proteomics raw “data can be reprocessed with new questions in mind, such as examining different post-translational modifications than the original study.” In our view, this will be the main contribution to biology arising from the reprocessing of raw data. A…
degradation

CELLULAR FUNCTIONS

cellular localization: mitochondrial
biological function: 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.

• Enzymes

REGULATION

Kinetic studies revealed significant differences in the K:(m) values obtained for alpha-ketoglutarate and glutamate for the GLUD1- and the GLUD2-derived GDH, with the allosteric activators differentially altering these values.

DIAGNOSTIC USE