Insulin and glucagon's reciprocal mediation of a dual regulation mechanism for pyruvate kinase.
The addition of glucagon to hepatocytes in primary culture produced a rapid and sustained increase in the Km (1.27 mM phosphoenol pyruvate) of pyruvate kinase. The low Km (0.4 mM) form of the enzyme was seen when cells were retreated with insulin, demonstrating a short-term regulation mechanism. Injections of insulin, glucagon or glucagon followed by insulin demonstrated that a similar mechanism occurs in vivo. Results from longer times after injection indicated that another mechanism occurs when altered activity was the result of changes in V max and not Km. Thus, a dual mechanism for regulation of pyruvate kinase occurs. A rapid responding system functions by modification of the enzyme, while a long-term system functions by altering the rate of synthesis, thus changing the amount of enzyme present.
D000818:Animals; D002478:Cells, Cultured; D005934:Glucagon / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology*; D007700:Kinetics; D008099:Liver / Q000201:enzymology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011770:Pyruvate Kinase / Q000378:metabolism*
D007328:Insulin; D005934:Glucagon; D011770:Pyruvate Kinase