REGULATION OF LIVER-METABOLISM BY CELL SW ELLING

Liver swelling caused by incubating hepatocytes in hypotonic media or with amino acids that are co-transported with sodium ion stimulates gl ycogen synthesis and lipogenesis, and inhibits proteolysis. Thus, live r swelling can be regarded as an anabolic signal. The signal transduct ion for glycogen synthesis and lipogenesis involves changes in ionic c omposition of the cells that follow cell swelling, and leads to the ac tivation of glycogen synthase and acetyl-CoA carboxylase, the rate-con trolling enzymes in these pathways. The ionic changes result from the accumulation of metabolites of amino acids and from the cellular respo nse to swelling which causes the extrusion of KCl. These ionic changes stimulate the protein phosphatase(s) responsible for the activation o f glycogen synthase and acetyl-CoA carboxylase.