Studies of Lipid Peroxidation, its Link to Human Pathologies, and Isotopic Reinforcement of Polyunsaturated Fatty Acids as a Strategy to Reduce Oxidative Damage

Abstract

Lipids are loosely defined as a group of naturally occurring organic compounds which are hydrophobic or amphipathic in nature, but which are also readily soluble in organic solvents. These solubility features are present in an extremely heterogeneous collection of molecules such as fatty acids, phospholipids, eicosanoids, and sterols. The functions of various lipids are diverse and wide ranging, and many are considered essential for standard life functions. Despite their importance within biological processes, many lipids are also susceptible to free radical oxidation and degradation in the presence of reactive oxygen species. This lipid oxidation, commonly referred to as lipid peroxidation, can have extensive physiological consequences and can play a role in the progression of human disease states such as Parkinson’s disease and atherosclerosis. The focus of this dissertation is centered around the free radical oxidation of polyunsaturated fatty acids (PUFAs). We present several kinetic studies probing the rates at which these reactions occur are reported for a wide variety of PUFAs and sterols. We also highlight physical studies involving isotopically reinforced polyunsaturated fatty acids and assess their ability to reduce levels of free radical oxidation both in solution and in biological systems.