Effects of low-level lead on glycolytic enzymes and pyruvate dehydrogenaseof rat brain in vitro: relevance to sporadic Alzheimer's disease?

Lead is known to be a potent inhibitor of many enzymes working in the brain , thus possibly inducing functional problems in the brain under pathophysio logical conditions. Among such enzymes are those involved in glucose metabo lism and energy production. We investigated the inhibitory effects of low-l evel lead on brain hexokinase (HK), glyceraldehyde-3-phosphate dehydrogenas e (GAPDH, pyruvate kinase (PK) and pyruvate dehydrogenase complex (PDHc) wi th rat brain homogenate. PDHc was distinctively inhibited when low-dose lea d acetate was added last of all (IC50 = 5 mu M) to the reaction mixture. Th e other enzymes were completely resistant to 5 mu M of lead acetate. When t he homogenate was preincubated with lead acetate HK was dramatically inhibi ted by low-level lead acetate (1-5 mu M), in a manner dependent on both pre incubation time and lead concentration. However, the inhibitory effect was abolished by coincubation with its substrates, glucose or ATP. The results suggest that exposure to low levels of lead may increase the risk of cerebr al hypometabolism caused by direct inhibition of specific glucose-utilizing enzymes. In this context, lead might be regarded as a risk factor in the a bnormal glucose metabolism seen in some kinds of neurodegenerative disorder s such as sporadic Alzheimer's disease.