Enzymes of the Fructose 6-Phosphate-Fructose 1, 6-Bisphosphate Substrate Cycle

This chapter discusses the regulation of enzyme activities of 6-phosphofructo-1-kinase, fructose-1,6-bisphosphatase, and 6-phosphofructo-2-kinase-fructose-2,6-bisphosphatase, with particular emphasis on the role of phosphorylation. Only in a few instances, phosphorylation–dephosphorylation has been shown to regulate an enzyme involved in the interconversion between fructose 6-phosphate and fructose 1,6-phosphate in a physiologically relevant way. The best example is regulation of hepatic 6-phosphofructo-2-kinase-fructose-2,6-bisphosphatase. The phosphorylation of this enzyme by the cyclic AMP-dependent protein kinase with resulting changes in the enzyme activities has been well characterized in vitro using purified preparations. Similar reciprocal changes in the enzyme activities have been demonstrated both in vivo and in isolated liver systems in response to elevated levels of cyclic adenosine monophosphate (AMP). There is also preliminary evidence that 6-phosphofructo-2-kinase in yeast and heart is regulated by phosphorylation. However, in neither case has the 6-phosphofructo-2-kinase been purified to homogeneity and its regulatory properties and in vitro phosphorylation studied in detail. With regard to regulation by phosphorylation, the enzymes in yeast and heart are different from that found in the liver. Mammalian 6-phosphofructo-1-kinase from the heart and skeletal muscle has been shown to contain covalently bound phosphate in vivo and to be substrates for the cyclic AMP-dependent protein kinase in vitro. It has been reported in the chapter that the muscle enzyme from Ascaris suum is activated by phosphorylation catalyzed by the cyclic AMP-dependent protein kinase. In Saccharomyces cerevisiae, cyclic AMP-dependent phosphorylation of fructose-1,6-bisphosphatase appears to play a role in catabolite repression leading to a decrease in enzyme activity and acting as a signal for proteolytic degradation.