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EFFECT OF LEAD ON GAMMA AMINO BUTYRIC ACID SYNTHESIS
Citation:
Moses, H. EFFECT OF LEAD ON GAMMA AMINO BUTYRIC ACID SYNTHESIS. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/1-78/009.
Description:
The project studies the inhibitory effect of lead on the enzymatic activity of brain glutamic amino acid decarboxylase (GADC). The enzyme is responsible for the catalytic formation of gamma amino butyric acid (GABA) inhibitory neurons which is believed to be involved with the transmission of inhibitory impulses in the brain. Lead nitrate solution was available to Sprague-Dawley female rats ad libitum and the quantity of lead ingested was determined by the volumes consumed. During the course of these experiments, animals were examined for weight loss, activity, and excitability and other behavioral manifestations of lead toxicity. At autopsy, the tissues selected for lead determinations were brain, liver, bone (femur). In another series of experiments GADC was isolated from fresh bovine brain tissue, and in vitro studies were performed to determine the nature of lead inhibition of the enzyme. Subsequently, Se and Cd inhibition of the enzyme were studied and compared to lead inhibition. The activity of the enzyme GADC in brain tissue homogenates of rats drinking lead nitrate solutions was less than the activity determined in control rats. When the inhibiting effect of Pb, Cd, and Se on GADC activity were compared, Pb proved to be the most potent inhibitor, while Cd showed less inhibition, showed no inhibition of enzyme activity.