Hormonal control of hepatic glutaminase.
(1) Glucagon activates hepatic glutaminase in vivo. Mitochondria from glucagon-injected rats retain an enhanced capacity to catabolize glutamine and this is more sensitive to activation by inorganic phosphate. The glucagon-elicited stimulation of glutaminase is not evident in broken mitochondria. A similar activation of glutaminase occurs in a number of situations which are associated with elevated glucagon levels in vivo, i.e., after a high-protein meal, after injection of bacterial endotoxin and in diabetes mellitus. (2) Studies in isolated hepatocytes revealed that glutaminase could be activated, not only by glucagon, but also by a cell-permeable protein kinase A activator (Sp-cAMPS) and by a cell-permeable protein phosphatase 1 and 2A inhibitor (okadaic acid). However, the activation of glutaminase by glucagon was not inhibited by a cell-permeable protein kinase A inhibitor (Rp-8-Br-cAMPS). We suggest that the signalling pathway, for glutaminase activation by glucagon, is complex and possibly contains redundant elements.
Brosnan
J T
JT
Department of Biochemistry, Memorial University of Newfoundland, St. John's, Canada.
Ewart
H S
HS
Squires
S A
SA
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology; D004044:Dietary Proteins / Q000008:administration & dosage; D004731:Endotoxins / Q000633:toxicity; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004988:Ethers, Cyclic / Q000494:pharmacology; D005934:Glucagon / Q000494:pharmacology*; D018698:Glutamic Acid / Q000096:biosynthesis; D005972:Glutaminase / Q000378:metabolism*; D005973:Glutamine / Q000378:metabolism*; D008930:Mitochondria, Liver / Q000187:drug effects / Q000201:enzymology*; D019319:Okadaic Acid; D010710:Phosphates / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction; D013873:Thionucleotides / Q000494:pharmacology
D004044:Dietary Proteins; D004731:Endotoxins; D004791:Enzyme Inhibitors; D004988:Ethers, Cyclic; D010710:Phosphates; D013873:Thionucleotides; D005973:Glutamine; D019319:Okadaic Acid; D015124:8-Bromo Cyclic Adenosine Monophosphate; C016957:adenosine-3',5'-cyclic phosphorothioate; D018698:Glutamic Acid; D005934:Glucagon; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D005972:Glutaminase