Pyruvate kinase and the interaction of amino acid and carbohydrate metabolism in solid tumors.

The interaction between glycolysis, glutaminolysis and tumor growth in WAG/Fra rnu/rnu rats has been investigated. Small tumors are characterized by a low conversion of glucose to lactate whereas the conversion of glutamine to lactate is high. In medium sized tumors the flow of glucose to lactate as well as oxygen utilization are increased whereas glutamine and serine consumption are reduced. At this stage the tumor cells start with glutamate and alanine production. Large tumors are characterized by a low oxygen and glucose supply but a high glucose and oxygen utilization rate. The conversion of glucose to glycine, alanine, glutamate, glutamine, and proline reaches high values and the amino acids are released. Pyruvate kinase increases with tumor weight and is positively correlated with an increase in glucose and oxygen utilization. The shift from glutamate consumption to glutamate production is correlated with an increase in glutamate dehydrogenase and glutamate oxaloacetate transaminase activity.