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

Abstract

The activities of ATP-citrate lyase in frog, guinea pig, mouse, rat, and human brain vary from 18 to 30 mu mol/h/g of tissue, being several times higher than choline acetyltransferase activity. Activities of pyruvate dehydrogenase and acetyl coenzyme A synthetase in rat brain are 206 and 18.4 mu mol/h/g of tissue, respectively. Over 70% of the activities of both choline acetyltransferase and ATP-citrate lyase in secondary fractions are found in synaptosomes. Their preferential localization in synaptosomes and synaptoplasm is supported by RSA 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 about 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 indicate that this enzyme is not a rate limiting step in the synthesis of the acetyl moiety of ACh in brain.

Acetyl-CoA the Key Factor for Survival or Death of Cholinergic Neurons in Course of Neurodegenerative Diseases

“…The highest activity of PDHC was found in the hippocampus and the lowest one (60 % lower) in the medulla oblongata [1, 2]. These PDHC patterns did not correlate with differential regional distribution of ChAT activities [2, 3]. It might result form the fact that cholinergic neurons form small about 1 % fractions of entire brain cell population.…”

“…However, activities of PDHC in different brain regions displayed no correlations with distribution specific markers of cholinergic pericarya and/or terminals [2, 3, 25]. Also, differentiation of SN56 cholinergic cells was accompanied by the decrease but not increase of PDHC activity [26, 27].…”

“…1). On the other hand, during postnatal development the increase of ChAT activity in cerebrum was accompanied by respective elevations in PDHC levels, what might be compatible with maturation-induced activation all transmitter systems [3, 28, 29]. …”

Effects of acute (−)-hydroxycitrate supplementation on substrate metabolism at rest and during exercise in humans

“…The knowledge that HCA could have an important effect on metabolism is not new-Sullivan and coworkers were already doing research on HCA in the 1970s (1-8). Although the clinical relevance of HCA as an effective antiobesity agent has often been proposed (1, 9-12), very little research has been performed to investigate the metabolic effects of HCA supplementation in vivo in humans.HCA is a competitive inhibitor of ATP-citrate lyase (EC 4.1.3.8), the enzyme catalyzing the extramitochondrial cleavage of citrate to oxaloacetate and acetyl-CoA (5,8,13,14). The action of HCA should reduce the acetyl-CoA pool, thus limiting the availability of 2-carbon units required for fatty acid and cholesterol biosynthesis.…”

Effects of Fat-Enriched Diet on the Content of Sphingolipids in the Brain and on Cognitive Functions in Old Rats

“…It should be noted that various cerebral regions are characterized by different intensities of metabolism of fatty acids [29]. The hippocampus and neocortex (the cerebral structures that are involved in the formation of memory and more intensely subjected to structural/functional modifications in the course of development of neurodegenerative diseases) are distinguished by an especially intense metabolism of these acids.…”