S E Knowles

Inactivation of Cytosol Enzymes by a Liver Membrane Protein

Non-proteolytic inactivation reactions have been suggested to play an important role in determining the relative rates of enzyme degradation within cells. An inactivation factor is present at high specific activity in hepatocyte plasma membrane which inactivates cytosol enzymes at rates roughly proportional to their rates of degradation in vivo. This factor has been purified about 100-fold and has similar catalytic selectivity to the crude factor. The inactivation reaction is accelerated by disulphide compounds and can be partially reversed by thiols. Furthermore, inactivation of enzymes is accompanied by a loss of measurable thiols in the enzymes. From these experiments it is concluded that the inactivation factor carries out a disulphide attack on surface thiol groups in cytosol enzymes leading to the formation of mixed disulphides which have lost catalytic activity. The inactive enzymes may be substrates for lysosomal or non-lysosomal proteolysis.