Regional and Subcellular Distribution of ATP‐Citrate Lyase and Other Enzymes of Acetyl‐CoA Metabolism in Rat Brain

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Abstract
The activities of ATP citrate lyase in frog, guinea pig, mouse, rat and human brain vary from 18-30 .mu.mol/h per g of tissue, being several times higher than choline acetyltransferase activity. Activities of pyruvate dehydrogenase and acetyl CoA synthetase in rat brain are 206 and 18.4 .mu.mol/h per g of tissue, respectively. Over 70% of the activities of choline acetyltransferase and ATP citrate lyase in secondary fractions are found in synaptosomes. Their preferential localization in synaptosomes and synaptoplasm is supported by RSA [relative specific activity] values above 2. Acetyl CoA synthetase activity is located mainly in whole brain mitochondria (RSA, 2.33) and its activity in synaptoplasm is low (RSA, 0.25). The activities of pyruvate dehydrogenase, citrate synthase and carnitine acetyltransferase are present mainly in fractions C and Bp. No pyruvate dehydrogenase activity is found in synaptoplasm. Striatum, cerebral cortex and cerebellum contain similar activities of pyruvate dehydrogenase, citrate synthase, carnitine acetyltransferase, fatty acid synthetase and acetyl CoA hydrolase. Activities of acetyl CoA synthetase, choline acetyltransferase and ATP citrate lyase in cerebellum are .apprx. 10 and 4 times lower, respectively, than in other parts of the brain. These data indicate preferential localization of ATP citrate lyase in cholinergic nerve endings and that this enzyme is not a rate limiting step in the synthesis of the acetyl moiety of ACh in brain.