Modulation of protein function by isoketals and levuglandins

Abstract

Oxidative stress, defined as an increase in reactive oxygen species, leads to peroxidation of polyunsaturated fatty acids and generates a vast number of biologically active molecules, many of which might contribute in some way to health and disease. This chapter will focus on one specific class of peroxidation products, the levuglandins and isoketals (also called isolevuglandins). These gamma-ketoaldehydes are some of the most reactive products derived from the peroxidation of lipids and exert their biological effects by rapidly adducting to primary amines such as the lysyl residues of proteins. The mechanism of their formation and remarkable reactivity will be described, along with evidence for their increased formation in disease conditions linked with oxidative stress and inflammation. Finally, the currently known effects of these gamma-ketoaldehydes on cellular function will then be discussed and when appropriate compared to the effects of alpha,beta-unsaturated fatty aldehydes, in order to illustrate the significant differences between these two classes of peroxidation products that modify proteins.