Hormonal regulation of acetyl-CoA carboxylase activity in the liver cell.
Chick liver cell monolayers synthesize fatty acids at in vivo rates and are responsive to insulin and glucagon. High rates of fatty acid synthesis are maintained with insulin present and lost slowly without insulin. Glucagon or 3',5'-cyclic AMP cause immediate cessation of fatty acid synthesis. The site of inhibition appears to be cytoplasmic acetyl-CoA carboxylase which catalyzes the first committed step of fatty acid synthesis. Liver carboxylase exists either as catalytically inactive protomers or active filamentous polymers. Citrate, an allosteric activator of the enzyme, is required for both catalysis and polymerization. Glucagon and cAMP cause an immediate decrease in the cytoplasmic citrate concentration of chick liver cells apparently by inhibiting the conversion of glucose to citrate at the phosphofructokinase reaction. Since fatty acid synthesis and citrate level are closely correlated, citrate appears to be a feed-forward activator of the carboxylase in vivo. Compelling evidence indicates that carboxylase filaments are present in the intact cell when citrate levels are high and depolymerize when citrate levels fall. Hence, carboxylase activity and fatty acid synthetic rate appear to be determined by cytoplasmic citrate level.
D000103:Acetyl-CoA Carboxylase / Q000378:metabolism*; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002645:Chickens; D002784:Cholesterol / Q000096:biosynthesis; D002951:Citrates / Q000378:metabolism; D064429:Fatty Acid Synthases / Q000378:metabolism; D005227:Fatty Acids / Q000096:biosynthesis; D005934:Glucagon / Q000494:pharmacology; D005989:Glycerides / Q000096:biosynthesis; D007659:Ketones / Q000096:biosynthesis; D008025:Ligases / Q000378:metabolism*; D008099:Liver / Q000166:cytology / Q000201:enzymology*
D002951:Citrates; D005227:Fatty Acids; D005989:Glycerides; D007659:Ketones; D003994:Bucladesine; D005934:Glucagon; D002784:Cholesterol; D064429:Fatty Acid Synthases; D008025:Ligases; D000103:Acetyl-CoA Carboxylase