Molecular and cellular regulation of pyruvate kinase in red blood cells.

The main sources of the heterogeneity of pyruvate kinase (PK) isoenzymes are discussed. The regulative role of the L-type PK for the energy metabolism of a tissue without glyconeogenesis has been examined in erythrocytes. For that purpose a kinetic model of the PK has been established taking into account the substrates and the effectors ATP and fructose-1,6.biphosphate. This PK model was incorporated into a complex mathematical model of glycolysis and the concentrations of metabolites and the glycolytic flux were calculated for normal PK activity and for a PK activity ten times lower than normal. From calculations it is concluded that under the conditions of PK deficiency the energy metabolism cannot be stabilized. This corresponds to the experimental finding that the filtration constant of PK deficient red blood cells increases with declining survival time.