Editing Pyruvate kinase (section)

=== Hormonal control ===
In order to prevent a [[futile cycle]], glycolysis and gluconeogenesis are heavily regulated in order to ensure that they are never operating in the cell at the same time. As a result, the inhibition of pyruvate kinase by glucagon, cyclic AMP and epinephrine, not only shuts down glycolysis, but also stimulates gluconeogenesis. Alternatively, insulin interferes with the effect of glucagon, cyclic AMP and epinephrine, causing pyruvate kinase to function normally and gluconeogenesis to be shut down. Furthermore, glucose was found to inhibit and disrupt gluconeogenesis, leaving pyruvate kinase activity and glycolysis unaffected. Overall, the interaction between hormones plays a key role in the functioning and regulation of glycolysis and gluconeogenesis in the cell.<ref name="Feliú_1976">{{cite journal | vauthors = Feliú JE, Hue L, Hers HG | title = Hormonal control of pyruvate kinase activity and of gluconeogenesis in isolated hepatocytes | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 73 | issue = 8 | pages = 2762–6 | year = 1976 | pmid = 183209 | pmc = 430732 | doi = 10.1073/pnas.73.8.2762| bibcode = 1976PNAS...73.2762F | doi-access = free }}</ref>

==== Inhibitory effect of metformin ====
Metformin, or [[Metformin|dimethylbiguanide]], is the primary treatment used for type 2 diabetes. Metformin has been shown to indirectly affect pyruvate kinase through the inhibition of gluconeogenesis. Specifically, the addition of metformin is linked to a marked decrease in glucose flux and increase in lactate/pyruvate flux from various metabolic pathways. Although metformin does not directly affect pyruvate kinase activity, it causes a decrease in the concentration of ATP. Due to the allosteric inhibitory effects of ATP on pyruvate kinase, a decrease in ATP results in diminished inhibition and the subsequent stimulation of pyruvate kinase. Consequently, the increase in pyruvate kinase activity directs metabolic flux through glycolysis rather than gluconeogenesis.<ref name="Argaud_1993">{{cite journal | vauthors = Argaud D, Roth H, Wiernsperger N, Leverve XM | title = Metformin decreases gluconeogenesis by enhancing the pyruvate kinase flux in isolated rat hepatocytes | journal = European Journal of Biochemistry | volume = 213 | issue = 3 | pages = 1341–8 | year = 1993 | pmid = 8504825 | doi = 10.1111/j.1432-1033.1993.tb17886.x | doi-access = free }}</ref>