The text discusses the role of protein oxidation in aging and its relationship with enzyme degradation. It begins by explaining that oxygen free radicals contribute to the oxidative modification of proteins, which marks enzymes for degradation by proteases. This process increases with age and in various diseases, possibly due to the accumulation of unrepaired DNA damage. The text also highlights that free radical damage to proteins has been less studied compared to damage to nucleic acids and lipids, though recent research suggests it may also contribute to aging. The two-step mechanism of enzyme degradation involves oxidation followed by degradation by proteases. Metal-catalyzed oxidation (MCO) systems generate hydrogen peroxide and Fe²⁺, which can oxidize amino acid residues in proteins. This leads to the formation of carbonyl derivatives, which can be used as a measure of protein damage. The site-specific nature of these reactions is confirmed by studies on enzymes like glutamine synthetase (GS), where specific amino acid residues are modified. The text also discusses the relationship between protein oxidation and aging, noting that oxidized proteins accumulate with age and may contribute to the loss of physiological function. Studies show that the amount of oxidized protein increases with age in various tissues, including human erythrocytes, fibroblasts, and brain tissue. The accumulation of oxidized protein is linked to the loss of enzyme activity and the inability to degrade oxidized proteins. The text further explores the physiological significance of oxidized protein accumulation, noting that it can impair cellular integrity and lead to age-related diseases. It also discusses the potential reversal of some age-related changes through the use of radical spin traps like PBN, which can reduce oxidized protein levels and restore enzyme activity. However, these effects are not permanent, suggesting that genetic factors may play a role in aging. The text concludes by emphasizing the importance of understanding the molecular basis of oxidized protein accumulation and its role in aging, as well as the potential for pharmacological interventions to mitigate age-related disorders.The text discusses the role of protein oxidation in aging and its relationship with enzyme degradation. It begins by explaining that oxygen free radicals contribute to the oxidative modification of proteins, which marks enzymes for degradation by proteases. This process increases with age and in various diseases, possibly due to the accumulation of unrepaired DNA damage. The text also highlights that free radical damage to proteins has been less studied compared to damage to nucleic acids and lipids, though recent research suggests it may also contribute to aging. The two-step mechanism of enzyme degradation involves oxidation followed by degradation by proteases. Metal-catalyzed oxidation (MCO) systems generate hydrogen peroxide and Fe²⁺, which can oxidize amino acid residues in proteins. This leads to the formation of carbonyl derivatives, which can be used as a measure of protein damage. The site-specific nature of these reactions is confirmed by studies on enzymes like glutamine synthetase (GS), where specific amino acid residues are modified. The text also discusses the relationship between protein oxidation and aging, noting that oxidized proteins accumulate with age and may contribute to the loss of physiological function. Studies show that the amount of oxidized protein increases with age in various tissues, including human erythrocytes, fibroblasts, and brain tissue. The accumulation of oxidized protein is linked to the loss of enzyme activity and the inability to degrade oxidized proteins. The text further explores the physiological significance of oxidized protein accumulation, noting that it can impair cellular integrity and lead to age-related diseases. It also discusses the potential reversal of some age-related changes through the use of radical spin traps like PBN, which can reduce oxidized protein levels and restore enzyme activity. However, these effects are not permanent, suggesting that genetic factors may play a role in aging. The text concludes by emphasizing the importance of understanding the molecular basis of oxidized protein accumulation and its role in aging, as well as the potential for pharmacological interventions to mitigate age-related disorders.