SELECTIVE-INHIBITION OF THE SYNTHESIS OF PHOSPHOENOL PYRUVATE CARBOXYKINASE IN FRESHLY ISOLATED PROXIMAL TUBULE CELLS

The behaviour of renal phospho enol pyruvate carboxykinase (PEPCK) in non-growing kidney cell suspension culture was investigated. In heterogeneous kidney cells, glomeruli-proximal tubule mixtures and purified proximal tubule fragments, the enzyme activity fell with a t1/2 of 3.3 h. Hormonal additions did not modify the process. The fall was also observed in cells prepared from animals preinduced with dexamethasone. The in vitro response of PEPCK is tissue specific. The decline was not the result of a decrease in cell viability, enzyme leakage nor due to the mitochondrial translocation of cytosolic PEPCK. The response observed is due to the selective inhibition of the synthesis of the enzyme and its destruction by non-lysosomal mechanisms. Acute and chronic acidification do not affect PEPCK activity. However, the degradation of PEPCK is temperature dependent and is greatly accelerated by glutathione.