Modification of proteins by reactive lipid oxidation products and biochemical effects of lipoxidation

Abstract

Lipid oxidation results in the formation of many reactive products, such as small aldehydes, substituted alkenals, and cyclopentenone prostaglandins, which are all able to form covalent adducts with nucleophilic residues of proteins. This process is called lipoxidation, and the resulting adducts are called advanced lipoxidation end products (ALEs), by analogy with the formation of advanced glycoxidation end products from oxidized sugars. Modification of proteins by reactive oxidized lipids leads to structural changes such as increased β-sheet conformation, which tends to result in amyloid-like structures and oligomerization, or unfolding and aggregation. Reaction with catalytic cysteines is often responsible for the loss of enzymatic activity in lipoxidized proteins, although inhibition may also occur through conformational changes at more distant sites affecting substrate binding or regulation. On the other hand, a few proteins are activated by lipoxidation-induced oligomerization or interactions, leading to increased downstream signalling. At the cellular level, it is clear that some proteins are much more susceptible to lipoxidation than others. ALEs affect cell metabolism, protein–protein interactions, protein turnover via the proteasome, and cell viability. Evidence is building that they play roles in both physiological and pathological situations, and inhibiting ALE formation can have beneficial effects.

Publication DOI: https://doi.org/10.1042/EBC20190058
Divisions: College of Health & Life Sciences > School of Biosciences
College of Health & Life Sciences
College of Health & Life Sciences > Chronic and Communicable Conditions
College of Health & Life Sciences > Aston Pharmacy School
College of Health & Life Sciences > School of Biosciences > Cellular and Molecular Biomedicine
Additional Information: © 2019 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.
Uncontrolled Keywords: Lipid oxidation,cytoskeleton,lipoxidation,post translational modification,protein unfolding,redox signalling,Biochemistry,Molecular Biology
Full Text Link:
Related URLs: https://portlan ... -of-proteins-by (Publisher URL)
http://www.scop ... tnerID=8YFLogxK (Scopus URL)
PURE Output Type: Review article
Published Date: 2020-02-17
Published Online Date: 2019-12-23
Accepted Date: 2019-11-27
Authors: Spickett, Corinne (ORCID Profile 0000-0003-4054-9279)
Pitt, Andrew (ORCID Profile 0000-0003-3619-6503)

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