title: Role of AMP on the activation of glycogen synthase and phosphorylase by adenosine, fructose, and glutamine in rat hepatocytes.
abstract: The mechanism for glycogen synthesis stimulation produced by adenosine, fructose, and glutamine has been investigated. We have analyzed the relationship between adenine nucleotides and glycogen metabolism rate-limiting enzymes upon hepatocyte incubation with these three compounds. In isolated hepatocytes, inhibition of AMP deaminase with erythro-9-(2-hydroxyl-3nonyl)adenine further increases the accumulation of AMP and the activation of glycogen synthase and phosphorylase by fructose. This ketose does not increase cyclic AMP or the activity of cyclic AMP-dependent protein kinase. Adenosine raises AMP and ATP concentration. This nucleotide also activates glycogen synthase and phosphorylase by covalent modification. The correlation coefficient between AMP and glycogen synthase activity is 0.974. Nitrobenzylthioinosine, a transport inhibitor of adenosine, blocks (by 50%) the effect of the nucleoside on AMP formation and glycogen synthase but not on phosphorylase. 2-Chloroadenosine and N6-phenylisopropyladenosine, nonmetabolizable analogues of adenosine, activate phosphorylase (6-fold) without increasing the concentration of adenine nucleotides or the activity of glycogen synthase. Cyclic AMP is not increased by adenosine in hepatocytes from starved rats but is in cells from fed animals. [Ethylenebis (oxyethylenenitrilo)]tetraacetic acid (EGTA) blocks by 60% the activation of phosphorylase by adenosine but not that of glycogen synthase. Glutamine also increases AMP concentration and glycogen synthase and phosphorylase activities, and these effects are blocked by 6-mercaptopurine, a purine synthesis inhibitor. Neither adenosine nor glutamine increases glucose 6-phosphate. It is proposed that the observed efficient glycogen synthesis from fructose, adenosine, and glutamine is due to the generation of AMP that activates glycogen synthase probably through increases in synthase phosphatase activity. It is also concluded that the activation of phosphorylase by the above-mentioned compounds can be triggered by metabolic changes.
authors.affiliation: Department of Biochemistry and Molecular Biology, Autonomous University of Barcelona, Bellaterra, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Carabaza
authors.forename: M D
authors.initials: MD
authors.lastname: Ricart
authors.forename: A
authors.initials: A
authors.lastname: Mor
authors.forename: J J
authors.initials: JJ
authors.lastname: Guinovart
authors.forename: C J
authors.initials: CJ
authors.lastname: Ciudad
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000241:Adenosine / Q000494:pharmacology*; D000244:Adenosine Diphosphate / Q000494:pharmacology; D000249:Adenosine Monophosphate / Q000494:pharmacology* / Q000502:physiology; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D004789:Enzyme Activation; D005632:Fructose / Q000494:pharmacology*; D005973:Glutamine / Q000494:pharmacology*; D006006:Glycogen Synthase / Q000378:metabolism*; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D008954:Models, Biological; D010762:Phosphorylase a / Q000378:metabolism; D006005:Phosphorylases / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D005973:Glutamine; D005632:Fructose; D000249:Adenosine Monophosphate; C010192:9-(2-hydroxy-3-nonyl)adenine; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D010762:Phosphorylase a; D006005:Phosphorylases; D006006:Glycogen Synthase; D000225:Adenine; D000241:Adenosine