Allosteric control of 6-phosphofructo-1-kinase from rat lung

1. The regulation of 6-phosphofructo-1-kinase (PFK) in the rat lung of normally fed (control), 72 hr-starved and streptozotocin-induced diabetic rats was investigated. 2. No significant changes in the total enzyme activities and the activity ratios [activity at 0.5 mM fructose 6-phosphate at pH 7.0/activity at pH 8.0 (v0.5/V)] of rat lung were observed between the control and 72 hr-starved or streptozotocin-induced diabetic rats. 3. Rat lung PFK was highly stimulated by fructose 2,6-bisphosphate (Fru-2,6-P2) as the affinity of the enzyme for fructose 6-phosphate was highly increased by this metabolite and the enzyme inhibition by ATP was released. 4. Although rat liver and mucosal PFK were found to be highly sensitive to stimulation by Fru-2,6-P2, lung PFK was significantly more sensitive to the stimulation by this metabolite than the other tissues. 5. The enzyme was highly inhibited by citrate and was only slightly inhibited by phosphocreatine. 6. ADP, AMP and c-AMP were shown to be activators of lung PFK with c-AMP being the most effective activator. 7. As a rate limiting enzyme of glycolysis, rat lung PFK is highly controlled by its allosteric effectors, especially Fru-2,6-P2, possibly for surfactant lipid synthesis which usually requires a high rate of glycolysis.