Impact of amino acid derivative osmolytes on structure-function integrity and aggregation propensity of catalase: Implications for inefficient antioxidant defense in protein aggregation disorders

Compelling evidence of co-existence of oxidative stress and altered osmolyte levels, particularly the amino acid derivatives, emphasizes the importance of accumulation of these stress protectant molecules. In this context, the present study investigated the impact of three key amino acid derivative osmolytes – taurine, N-acetylcysteine (NAC), and N-acetylaspartate (NAA) – on the catalytic activity, structural integrity, stability and aggregation propensity of catalase, an important antioxidant enzyme. Results obtained in kientic studies revealed a concentration-dependent decrease in the catalytic activity of catalase in the presence of these osmolytes, with NAC exhibiting the most significant reduction in kinetic parameters. Structural studies revealed that all the three osmolytes induced alterations in the tertiary and secondary structure of catalase with increased β-sheet and β-turn content leading to enhanced aggregation propensity, transmission electron microscopy results confirmed the presence of catalase aggregates in the osmolyte-treated samples of catalase. Collectively, our results suggest that taurine, NAC, and NAA reduced catalase activity with distorted structure while promoting aggregation, providing new insights into the modulatory effects of amino acid derivative osmolytes on the structure-function integrity and stability of antioxdiant enyzme, catalase. The observed results might have implications for understanding the role of metabolite osmolyte in the mechanistics of oxidative stress-related diseases and other protein aggregation disorders.