Protein Antioxidant Response to the Stress and the Relationship between Molecular Structure and Antioxidant Function

BACKGROUND Proteins have long been considered a principal target for oxidants as a result of their abundance in biological systems. However, there is increasing evidence about the significant antioxidant activity in proteins such as albumin. It is leading to new concepts that even consider albumin not only as an antioxidant but as the major antioxidant in plasma known to be exposed to continuous oxidative stress. Evidence presented here establishes a previously unrecognized relationship between proteins' antioxidant capacity and structural stress. METHODOLOGY/PRINCIPAL FINDINGS A chemiluminiscence based antioxidant assay was achieved to quantify the antioxidant capacity of albumin and other proteins. The capabilities of proteins as antioxidants were presented, but in addition a new and powerful component of the protein antioxidant capacity was discovered. The intrinsic component, designated as Response Surplus (RS), represents a silent reserve of antioxidant power that awakens when proteins face a structural perturbation (stressor) such as temperature, short wave UV light, the same reactive oxygen species, and more extreme changes like glucose or aldehyde-mediated structural modifications. The work also highlights the importance of structural changes in protein antioxidant properties and the participation of sulfhydryl groups (SHs) in the RS antioxidant component. Based on recent evidence about the SH group chemistry, a possible model for explaining RS is proposed. CONCLUSIONS/SIGNIFICANCE The data presented show the significant antioxidant behavior of proteins and demonstrate the existence of a previously unrecognized antioxidant response to the stress. Several implications, including changes in elementary concepts about antioxidants and protein function, should emerge from here.