Activation of glutamate apodecarboxylase by succinic semialdehyde and pyridoxamine 5'-phosphate.
Glutamate apodecarboxylase was activated by incubation with succinic semialdehyde and pyridoxamine 5'-phosphate. Activation required both compounds and was highly selective for succinic semialdehyde. Of 18 analogs tested, only glyoxylate, pyruvate, oxaloacetate, and 2-oxoglutarate activated the apoenzyme significantly, but much higher concentrations of these compounds than of succinic semialdehyde were required. In the presence of pyridoxamine 5'-phosphate, the concentration of succinic semialdehyde giving half-maximal activation of apoenzyme was 7 microM. In contrast, the Ki for succinic semialdehyde as a competitive inhibitor of glutamate decarboxylation was 1.2 mM, indicating that apoenzyme with bound pyridoxamine 5'-phosphate has a much higher affinity for succinic semialdehyde than does holoenzyme. The concentration of pyridoxamine 5'-phosphate giving half-maximal activation was 17 microM, which is more than an order of magnitude greater than the corresponding value for pyridoxal 5'-phosphate.
D001051:Apoenzymes / Q000378:metabolism*; D001059:Apoproteins / Q000378:metabolism*; D001667:Binding, Competitive; D004789:Enzyme Activation / Q000187:drug effects; D005968:Glutamate Decarboxylase / Q000378:metabolism*; D005971:Glutamates / Q000378:metabolism; D018698:Glutamic Acid; D006038:Glyoxylates / Q000494:pharmacology; D007656:Ketoglutaric Acids / Q000494:pharmacology; D007700:Kinetics; D010071:Oxaloacetates / Q000494:pharmacology; D011733:Pyridoxamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D011773:Pyruvates / Q000494:pharmacology; D019289:Pyruvic Acid; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives* / Q000494:pharmacology
D001051:Apoenzymes; D001059:Apoproteins; D005971:Glutamates; D006038:Glyoxylates; D007656:Ketoglutaric Acids; D010071:Oxaloacetates; D011773:Pyruvates; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D011733:Pyridoxamine; D019289:Pyruvic Acid; D005968:Glutamate Decarboxylase; C031150:glyoxylic acid; C009338:succinic semialdehyde; C010627:pyridoxamine phosphate