Case 1: Pyruvate Kinase (PK) catalyzes the rate-limiting,ATP-generating step of glycolysis in which phosphoenolpyruvate(PEP) is converted to pyruvate. Multiple isoenzymes of pyruvatekinase exist in mammals: type L, which is found in the liver andkidneys; type R, which is expressed in erythrocytes; type M1, whichis found in tissues such as muscle and brain; and type M2, which ispresent in self-renewing cells such as embryonic and adult stemcells. 1) Under normal conditions, describe all the ways in whichpyruvate kinase is regulated in the cell? Many types of cancercells are predominantly glycolytic and over express the oncoproteinMYC. Interestingly, the classical oncoprotein MYC has been found topromote preferential expression of pyruvate kinase type M2 overpyruvate kinase type M1. The isoform M2 is characteristically foundin a low activity state and is ineffective at promoting glycolysis(When compared to pyruvate kinase type L or type M1). 2) This logicseems counter-intuitive for a glycolytic tissue. What is therationale for this mechanism and what other pathways may cancercells be diverting substrate to?
