Regulation of rat liver 4-hydroxy-2-ketoglutarate aldolase

The possibility is examined that 4-hydroxy-2-ketoglutarate aldolase (4-hydroxy-2-ketoglutarate glyoxylatelyase, EC 4.1.3.16), the last step in hydroxyproline catabolism is regulated by intermediates of gluconeogenesis. Inhibition of isolated 4-hydoxy-2-ketoglutarate aldolase was examined using dual inhibition studies. It was found that the enzyme exhibits synergistic inhibition by oxaloacetate and pyruvate, but only when the substrate concentration is low. At substrate concentrations approaching saturation, the inhibition by the oxaloacetate and pyruvate becomes additive. These results are discussed in terms of possible control of the use of carbon from hydroxyproline breakdown in glucose production.