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Testing The Hypothesis That “Methionine Residues In Proteins Are Antioxidants”
Author(s) -
luo shen,
Levine Rodney L
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.758.1
Subject(s) - methionine sulfoxide , methionine , biochemistry , hydrogen peroxide , reactive oxygen species , chemistry , hypochlorous acid , glutamine , amino acid , hypochlorite , organic chemistry
A variety of reactive oxygen species (ROS) react readily with methionine (Met) residues to form methionine sulfoxide (MetO) and most cells contain methionine sulfoxide reductases that can reduce MetO back to Met. Thus, Met residues may serve as antioxidants and scavenge ROS. To investigate this hypothesis directly, we used an E. coli Met auxotroph to substitute Met with its analog norleucine (Nle), in which ‐CH2‐replaces the ‐S‐ of Met. Amino acid analysis of cellular proteins demonstrated an ~40% reduction of Met residues and equivalent increase in Nle. The intracellular free Met and S‐adenosylmethionine pools were not reduced by Nle substitution. The activity of glutamine synthetase was also unchanged in the cells grown on Nle, consistent with the prevalent view in the literature that protein function is little changed by substitution of Nle for Met. When challenging both cells with hypochlorite, hydrogen peroxide, or ionizing radiation, Nle‐containing cells died more rapidly than the control cells. Protein carbonyl levels were not significantly affected by these oxidative stresses, possibly because carbonyl levels are already elevated as a consequence of carbon starvation. MetO contents were also higher in Nle‐containing cells than in the control cells after hypochlorite and hydrogen peroxide challenges. Our results support the hypothesis that Met residues act as endogenous antioxidants in cells.