Serum electrolytes can promote hydroxyl radical-initiated biomolecular damage from inflammation

Yukako Komaki, Adam M.A. Simpson, Jong Kwon Choe, Margaux M. Pinney, Daniel Herschlag, Yi-Hsueh Chuang, William A. Mitch*


研究成果: Article同行評審

7 引文 斯高帕斯(Scopus)


Chronic inflammatory disorders are associated with biomolecular damage attributed partly to reactions with Reactive Oxygen Species (ROS), particularly hydroxyl radicals (OH). However, the impacts of serum electrolytes on ROS-associated damage has received little attention. We demonstrate that the conversion of OH to carbonate and halogen radicals via reactions with serum-relevant carbonate and halide concentrations fundamentally alters the targeting of amino acids and loss of enzymatic activity in catalase, albumin and carbonic anhydrase, three important blood proteins. Chemical kinetic modeling indicated that carbonate and halogen radical concentrations should exceed OH concentrations by 6 and 2 orders of magnitude, respectively. Steady-state γ-radiolysis experiments demonstrated that serum-level carbonates and halides increased tyrosine, tryptophan and enzymatic activity losses in catalase up to 6-fold. These outcomes were specific to carbonates and halides, not general ionic strength effects. Serum carbonates and halides increased the degradation of tyrosines and methionines in albumin, and increased the degradation of histidines while decreasing enzymatic activity loss in carbonic anhydrase. Serum electrolytes increased the degradation of tyrosines, tryptophans and enzymatic activity in the model enzyme, ketosteroid isomerase, predominantly due to carbonate radical reactions. Treatment of a mutant ketosteroid isomerase indicated that preferential targeting of the active site tyrosine accounted for half of the total tyrosine loss. The results suggest that carbonate and halogen radicals may be more significant than OH as drivers for protein degradation in serum. Accounting for the selective targeting of biomolecules by these daughter radicals is important for developing a mechanistic understanding of the consequences of oxidative stress.

頁(從 - 到)475-482
期刊Free Radical Biology and Medicine
出版狀態Published - 9月 2019


深入研究「Serum electrolytes can promote hydroxyl radical-initiated biomolecular damage from inflammation」主題。共同形成了獨特的指紋。