Biochemistry and pathology of radical-mediated protein oxidation
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Biochemistry and pathology of radical-mediated protein oxidation. / Dean, R T; Fu, S; Stocker, R; Davies, Michael Jonathan.
In: Biochemical Journal, Vol. 324 ( Pt 1), 1997, p. 1-18.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Biochemistry and pathology of radical-mediated protein oxidation
AU - Dean, R T
AU - Fu, S
AU - Stocker, R
AU - Davies, Michael Jonathan
PY - 1997
Y1 - 1997
N2 - Radical-mediated damage to proteins may be initiated by electron leakage, metal-ion-dependent reactions and autoxidation of lipids and sugars. The consequent protein oxidation is O2-dependent, and involves several propagating radicals, notably alkoxyl radicals. Its products include several categories of reactive species, and a range of stable products whose chemistry is currently being elucidated. Among the reactive products, protein hydroperoxides can generate further radical fluxes on reaction with transition-metal ions; protein-bound reductants (notably dopa) can reduce transition-metal ions and thereby facilitate their reaction with hydroperoxides; and aldehydes may participate in Schiff-base formation and other reactions. Cells can detoxify some of the reactive species, e.g. by reducing protein hydroperoxides to unreactive hydroxides. Oxidized proteins are often functionally inactive and their unfolding is associated with enhanced susceptibility to proteinases. Thus cells can generally remove oxidized proteins by proteolysis. However, certain oxidized proteins are poorly handled by cells, and together with possible alterations in the rate of production of oxidized proteins, this may contribute to the observed accumulation and damaging actions of oxidized proteins during aging and in pathologies such as diabetes, atherosclerosis and neurodegenerative diseases. Protein oxidation may also sometimes play controlling roles in cellular remodelling and cell growth. Proteins are also key targets in defensive cytolysis and in inflammatory self-damage. The possibility of selective protection against protein oxidation (antioxidation) is raised.
AB - Radical-mediated damage to proteins may be initiated by electron leakage, metal-ion-dependent reactions and autoxidation of lipids and sugars. The consequent protein oxidation is O2-dependent, and involves several propagating radicals, notably alkoxyl radicals. Its products include several categories of reactive species, and a range of stable products whose chemistry is currently being elucidated. Among the reactive products, protein hydroperoxides can generate further radical fluxes on reaction with transition-metal ions; protein-bound reductants (notably dopa) can reduce transition-metal ions and thereby facilitate their reaction with hydroperoxides; and aldehydes may participate in Schiff-base formation and other reactions. Cells can detoxify some of the reactive species, e.g. by reducing protein hydroperoxides to unreactive hydroxides. Oxidized proteins are often functionally inactive and their unfolding is associated with enhanced susceptibility to proteinases. Thus cells can generally remove oxidized proteins by proteolysis. However, certain oxidized proteins are poorly handled by cells, and together with possible alterations in the rate of production of oxidized proteins, this may contribute to the observed accumulation and damaging actions of oxidized proteins during aging and in pathologies such as diabetes, atherosclerosis and neurodegenerative diseases. Protein oxidation may also sometimes play controlling roles in cellular remodelling and cell growth. Proteins are also key targets in defensive cytolysis and in inflammatory self-damage. The possibility of selective protection against protein oxidation (antioxidation) is raised.
KW - Animals
KW - Free Radicals
KW - Humans
KW - Lipoproteins
KW - Macromolecular Substances
KW - Models, Chemical
KW - Oxidation-Reduction
KW - Protein Denaturation
KW - Protein Folding
KW - Proteins
KW - Reactive Oxygen Species
KW - Sulfhydryl Compounds
KW - Superoxides
M3 - Journal article
C2 - 9164834
VL - 324 ( Pt 1)
SP - 1
EP - 18
JO - Biochemical Journal
JF - Biochemical Journal
SN - 0264-6021
ER -
ID: 138285833