A temperature-sensitive change in the energy of activation of hormone-stimulated hepatic adenylyl cyclase.
We describe an abrupt increase (at 32 degrees ) in the energy of activation for the reaction of hepatic adenylyl cyclase in the presence of glucagon or epinephrine. This increase is not seen in the presence of fluoride, prostaglandin E(1), or 1-propanol, or in the absence of cyclase stimulators. The change in energy of activation found with hormones is abolished by 1-propanol. This change does not represent differences in hormone or substrate binding at different temperatures, but seems to reflect interactions among elements of the cyclase stimulation sequence. Similar changes in energy of activation were not observed for alkaline phosphatase, cyclic AMP-phosphodiesterase, 5'-nucleotidase, or ouabain-sensitive ATPase. Since the mole fraction of cholesterol in liver membranes is sufficiently high to preclude a phase change in bulk membrane lipids, our observation suggests either that cyclase is restricted to cholesterol-poor membrane regions or that the change in its energy of activation is largely restricted to protein components of the cyclase apparatus. The data are compatible with fundamental differences in the stimulation process(es) for the hormones (glucagon and epinephrine) as compared with those for fluoride and prostaglandin E(1).
D000433:1-Propanol / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000378:metabolism; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D002247:Carbon Isotopes; D000242:Cyclic AMP; D004789:Enzyme Activation / Q000187:drug effects; D004837:Epinephrine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D005260:Female; D005459:Fluorides / Q000494:pharmacology; D005934:Glucagon / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D007700:Kinetics; D008099:Liver / Q000201:enzymology*; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D011453:Prostaglandins / Q000494:pharmacology; D051381:Rats; D013696:Temperature; D014316:Tritium
D002247:Carbon Isotopes; D011453:Prostaglandins; D014316:Tritium; D000255:Adenosine Triphosphate; D005934:Glucagon; D000433:1-Propanol; D000242:Cyclic AMP; D000469:Alkaline Phosphatase; D010727:Phosphoric Diester Hydrolases; D000262:Adenylyl Cyclases; D005459:Fluorides; D004837:Epinephrine