Pyritinol and the enzymes of gamma-aminobutyric acid (GABA) synthesis and degradation.
Pyritinol, a vitamin B6 derivative considered to have an activating effect on brain inhibited glutamate decarboxylase in concentrations of 0.05-1.0 mmol/l. This effect was not dependent on the pyridoxal-5'-phosphate concentration. An increase in the glutamate level reduced the inhibitory effect of pyritinol, but inhibition was not competitive. It is supposed that this modification of inhibition of glutamate decarboxylase by the substrate concentration might be associated with the presence of two glutamate decarboxylases with different affinities for the substrate. The inhibitory effect of pyritinol was dependent on integrity of the disulphide bond in the pyritinol molecule. Inhibition of glutamate decarboxylase increased in correlation to time--possibly in association with progressive oxidation of the SH-groups of the enzyme. Pyritinol did not influence GABA transaminase activity, but lessened the oxidation of GABA to carbon dioxide. It is assumed that succinic semialdehyde dehydrogenase activity was inhibited.
Turský
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Department of Chemistry and Biochemistry, Faculty of Medicine, Comenius University, Bratislava.
D000612:4-Aminobutyrate Transaminase / Q000378:metabolism*; D000445:Aldehyde Oxidoreductases / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000201:enzymology; D005968:Glutamate Decarboxylase / Q000037:antagonists & inhibitors*; D007700:Kinetics; D008928:Mitochondria / Q000201:enzymology; D011725:Pyridines / Q000494:pharmacology*; D011732:Pyridoxal Phosphate / Q000494:pharmacology; D011746:Pyrithioxin / Q000494:pharmacology*; D051381:Rats; D050644:Succinate-Semialdehyde Dehydrogenase; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D011725:Pyridines; D005680:gamma-Aminobutyric Acid; D011732:Pyridoxal Phosphate; D011746:Pyrithioxin; D000445:Aldehyde Oxidoreductases; C493647:Aldh5a1 protein, rat; D050644:Succinate-Semialdehyde Dehydrogenase; D000612:4-Aminobutyrate Transaminase; D005968:Glutamate Decarboxylase