Reactive oxygen species and biological aging: a mechanistic approach.
The experimental evidence for an age-dependent increased generation of reactive oxygen species and a progressive accumulation of oxidized biomolecules is growing. However, despite such facts there is no detailed mechanistic information on how the higher availability of reactive oxygen species translates into the accumulation of oxidized biomolecules. For example, open questions are which reactive oxygen species are responsible for what types of oxidation products in vivo, under what specific reaction conditions can we expect which reaction products, and why specifically are modified biomolecules eliminated whereas others accumulate? Mitochondria appear to serve as the major source for reactive oxygen species in aging tissue. Genetic experiments have demonstrated an effect of Cu,ZnSOD on life span and in the prevention of age-related oxidative damage, suggesting that extramitochondrial superoxide promotes biological aging. However, as superoxide does not easily cross membranes, potential chemical pathways that convert mitochondrial reactive oxygen species into superoxide outside the mitochondria are displayed. The chemical reactivity of individual reactive oxygen species with the amino acid side chain of methionine is surveyed to obtain mechanistic details on the oxidation pathways potentially leading to the age-dependent methionine oxidation of the protein calmodulin in vivo. It will evolve that the in vivo accumulation of oxidized calmodulin cannot be the result of the reaction of an individual reactive oxygen species with calmodulin in homogenous solution alone. Complexation of calmodulin to calmodulin-binding proteins and protein turnover are additional parameters likely contributing to the accumulation of specifically modified calmodulin.
Schöneich
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Department of Pharmaceutical Chemistry, University of Kansas, Lawrence 66047, USA. schoneich@hbc.ukans.edu
D000375:Aging / Q000378:metabolism*; D000818:Animals; D002147:Calmodulin / Q000502:physiology; D006801:Humans; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism
D002147:Calmodulin; D017382:Reactive Oxygen Species; D013481:Superoxides