Regulation of liver lipase. I. Evidence for several regulatory sites, studied in corticotrophin-treated rats.
The activity of liver lipase, an enzyme that can be released from the liver by heparin, varies under several hormonal conditions. The site(s) at which regulation of the enzyme activity may occur was investigated in vitro. As a model, rats were used which had been treated with a corticotrophin analogue, to induce hypercortisolism, a condition in which liver lipase activity is lowered. Lipases isolated from heparin-containing perfusates of livers from ACTH or control rats were identical with respect to heat stability and specific activity as determined by immunotitration and binding to isolated non-parenchymal liver cells, indicating that the enzyme structure was not affected by the treatment. The secretion of liver lipase by isolated parenchymal liver cells was studied. During incubation of parenchymal cells derived from ACTH rats, less enzyme activity was found to be secreted when compared with hepatocytes isolated from control rats (ACTH rats, 2.30 +/- 0.2 mU/10(6) cells; control rats, 3.3 +/- 0.3 mU/10(6) cells). Liver lipase partially purified from control rats could be bound specifically to saturation by non-parenchymal cells, isolated from ACTH or control rats. Non-parenchymal cells from ACTH rats bound less lipase activity (29 mU/mg cell protein) than cells from control rats (50 mU/mg cell protein). This reduction in binding capacity seems to be due to a diminished number of binding sites, since the affinity based on Scatchard analysis and half-maximal binding was not different. These results suggest that the lowered liver lipase activity found during hypercortisolism may be due to an impaired synthesis and/or secretion of the enzyme by the parenchymal cells and to a reduced binding capacity of the non-parenchymal cells for liver lipase.
D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000818:Animals; D006493:Heparin / Q000494:pharmacology; D007700:Kinetics; D008049:Lipase / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D011485:Protein Binding; D051381:Rats; D011919:Rats, Inbred Strains
D000324:Adrenocorticotropic Hormone; D006493:Heparin; D008049:Lipase