Lipid peroxidation pathways (LPO)

Lipid peroxidation pathways represent a complex biochemical process involving the oxidative degradation of lipids, primarily polyunsaturated fatty acids (PUFAs) within cellular membranes. This process occurs via a free radical-mediated chain reaction consisting of initiation, propagation, and termination phases, often catalyzed by transition metals like iron or enzymes such as lipoxygenases [1.5.2]. The resulting lipid hydroperoxides decompose into highly reactive electrophilic aldehydes, including malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE), which can form damaging adducts with DNA and proteins [1.5.3]. While low levels of these products function in normal cell signaling and adaptive stress responses, their excessive accumulation is a hallmark of ferroptosis, a form of regulated non-apoptotic cell death [1.1.2]. Consequently, lipid peroxidation is implicated in the pathogenesis of numerous conditions, including neurodegenerative diseases, atherosclerosis, and ischemia-reperfusion injury [1.5.1]. Therapeutic strategies focus on either inhibiting these pathways using lipophilic antioxidants and iron chelators to protect healthy tissue or inducing them via GPX4 inhibition to selectively eliminate cancer cells [1.4.1].

Other names

Lipid peroxidationOxidative lipid degradationPolyunsaturated fatty acid peroxidationPUFA peroxidation

Drugs modulate lipid peroxidation by scavenging free radicals, chelating catalytic metal ions like iron, inhibiting key enzymes such as lipoxygenases or ACSL4, or depleting glutathione to induce ferroptosis in cancer cells [1.2.1, 1.4.1].