Question

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 pyruvate kinase exist in mammals: type L, which is found in the liver and kidneys; type R, which is expressed in erythrocytes; type M1, which is found in tissues such as muscle and brain; and type M2, which is present in self-renewing cells such as embryonic and adult stem cells. 1) Under normal conditions, describe all the ways in which pyruvate kinase is regulated in the cell? Many types of cancer cells are predominantly glycolytic and over express the oncoprotein MYC. Interestingly, the classical oncoprotein MYC has been found to promote preferential expression of pyruvate kinase type M2 over pyruvate kinase type M1. The isoform M2 is characteristically found in a low activity state and is ineffective at promoting glycolysis (When compared to pyruvate kinase type L or type M1). 2) This logic seems counter-intuitive for a glycolytic tissue. What is the rationale for this mechanism and what other pathways may cancer cells be diverting substrate to?

Answer 1