Covalent Modification of Proteins by Mixed Function Oxidation

Abstract

Publisher Summary This chapter discusses the covalent modification of proteins by mixed function oxidation. The work has revealed the powerful and intricate regulation mediated by covalent modification of enzymes. This chapter summarizes the most recently identified covalent modification of glutamine synthetase. Intracellular proteins undergo proteolytic degradation in a specific, regulated fashion; this is true for prokaryotic organisms and for complex mammals. Many proteins are susceptible to modification by one or more mixed function oxidation systems. The oxidative modification renders glutamine synthetase catalytically inactive; the physical changes in the protein are subtle. The oxidatively modified glutamine synthetase is more susceptible to attack by nonspecific proteases. If the modification is to serve as a marker for proteolytic degradation, then one must postulate the existence of proteases with notable specificity for oxidatively modified proteins. The specific activity of certain enzymes decreases with aging. The mechanisms that cause this change are unknown, but oxidative modification could be responsible. Oxidative changes in proteins result as a toxic side effect of oxygen therapy. Oxidative inactivation of enzymes serve to protect higher organisms from autolysis by lysosomal enzymes released from their own activated neutrophils.