Glutamate decarboxylase side reactions catalyzed by the enzyme


Correspondence to J. E. Churchich, Department of Biochemistry, University of Tennessee, Knoxville, Tennessee, USA 37996


A homogeneous glutamate decarboxylase isolated from pig brain contains 0.8 mol of tightly bound pyridoxal 5-phosphate/enzyme dimer. Upon addition of exogenous pyridoxal 5-phosphate (pyridoxal-5-P), the enzyme acquires maximum catalytic activity.

Preincubation of the enzyme with l-glutamate (10 mM) brings about changes in the absorption spectrum of bound pyridoxal-5-P with the concomitant formation of succinic semialdehyde. However, the rate of this slow secondary reaction, i.e. decarboxylative transamination, is 10−4 times the rate of normal decarboxylation. It is postulated that under physiological conditions enzymatically inactive species of glutamate decarboxylase, generated by the process of decarboxylative transamination, are reconstituted by pyridoxal-5-P produced by the cytosolic enzymes pyridoxal kinase and pyridoxine-5-P oxidase.

The catalytic activity of resolved glutamate decarboxylase is recovered by preincubation with phospho-pyridoxyl-ethanolamine phosphate. The experimental evidence is consistent with the interpretation that the resolved enzyme binds the P-pyridoxyl analog, reduces the stability of the covalent bond of the phospho-pyridoxyl moiety, and catalyzes the formation of pyridoxal-5-P.


phospho-pyridoxal-ethanolamine phosphate


Glutamate decarboxylase (EC


succinic semialdehyde dehydrogenase (EC


pyridoxine-5-phosphate oxidase (EC


aspartate aminotransferase (EC


pyridoxal kinase (EC