Transaminations catalysed by brain glutamate decarboxylase

Area of Science:

• Biochemistry
• Enzymology
• Neuroscience

Background:

• Glutamate decarboxylase (GAD) is crucial for synthesizing 4-aminobutyrate (GABA).
• GAD exists in multiple forms (alpha, beta, gamma) with varying activities.
• The enzyme utilizes pyridoxal 5'-phosphate (PLP) as a cofactor.

Purpose of the Study:

• To investigate the transamination activities of pig brain glutamate decarboxylase.
• To elucidate the role of transamination in holoenzyme inactivation and apoenzyme formation.
• To understand the physiological significance of GAD transamination in the brain.

Main Methods:

• Enzymatic assays measuring transamination rates with L-glutamate and 4-aminobutyrate.
• Characterization of enzyme kinetics across different pH values.
• Stoichiometric analysis of reaction products (succinic semialdehyde and pyridoxamine 5'-phosphate).

Main Results:

• GAD catalyzes both decarboxylation-dependent and direct transamination reactions.
• Transamination leads to the formation of succinic semialdehyde and pyridoxamine 5'-phosphate, converting holoenzyme to apoenzyme.
• Transamination rates varied among GAD forms and correlated with enzyme inactivation rates.

Conclusions:

• Transamination is a major pathway for glutamate decarboxylase apoenzyme formation.
• This reaction may explain the high proportion of apoenzyme observed in brain tissue.
• The findings suggest transamination is physiologically significant for GAD regulation.