The Action of Peroxyl Radicals, Powerful Deleterious Reagents, Explains Why Neither Cholesterol Nor Saturated Fatty Acids Cause Atherogenesis and Age‐Related Diseases

Abstract

Cells respond to alterations in their membrane structure by activating hydrolytic enzymes. Thus, polyunsaturated fatty acids (PUFAs) are liberated. Free PUFAs react with molecular oxygen to give lipid hydroperoxide molecules (LOOHs). In case of severe cell injury, this physiological reaction switches to the generation of lipid peroxide radicals (LOO(·)). These radicals can attack nearly all biomolecules such as lipids, carbohydrates, proteins, nucleic acids and enzymes, impairing their biological functions. Identical cell responses are triggered by manipulation of food, for example, heating/grilling and particularly homogenization, representing cell injury. Cholesterol as well as diets rich in saturated fat have been postulated to accelerate the risk of atherosclerosis while food rich in unsaturated fatty acids has been claimed to lower this risk. However, the fact is that LOO(·) radicals generated from PUFAs can oxidize cholesterol to toxic cholesterol oxides, simulating a reduction in cholesterol level. In this review it is shown how active LOO(·) radicals interact with biomolecules at a speed transcending usual molecule-molecule reactions by several orders of magnitude. Here, it is explained how functional groups are fundamentally transformed by an attack of LOO(·) with an obliteration of essential biomolecules leading to pathological conditions. A serious reconsideration of the health and diet guidelines is required.

Reactive Oxygen Species-Induced Lipid Peroxidation in Apoptosis, Autophagy, and Ferroptosis

“…Thus, the membrane phospholipids, containing high levels of PUFAs, are extremely sensitive to be attacked by ROS [30]. Moreover, the PUFAs themselves convert into reactive free radicals after reacting with the free radicals which are able to propagate lipid peroxidation chain reactions [31].…”

Redox Mechanisms in Neurodegeneration: From Disease Outcomes to Therapeutic Opportunities

“…The primary pathway of peroxyl radical, ROO , formation in biological systems is autoxidation viz. lipid peroxidation (419,480). Lipid peroxidation occurs when free radicals attack lipids containing carbon/carbon double bond(s), especially PUFAs.…”

Monitoring photo-oxidative and salinity-induced bacterial stress in the Canadian Arctic using specific lipid tracers

“…This activation involves the reaction of the native ferrous enzyme with hydroperoxides, thus affording an active ferric (Fe +3 ) enzyme and an alkoxyl radical (Garreta et al, 2013). As such, it is interesting to note that the generation of radicals during the iron-based catalytic cycle may also serve as a catalyst for autoxidation processes (Fuchs and Spiteller, 2014;Spiteller and Afzal, 2014). The simultaneous presence of high proportions of 10S-DOX-like lipoxygenase enzymatic (15%) and autoxidative (35%) palmitoleic acid oxidation products observed in surface sediments collected in spring 2015 ( Fig.…”

“…This conclusion is supported by relatively high values of trans/cis fatty acid ratios measured previously in Arctic surface sediments (Rontani et al, 2012), which indirectly attests to a strong contribution of sea ice material to high latitude sedimentary OM. However, due to the likely presence of 10S-DOX-like lipoxygenase enzymatic activity in seafloor sediments, and its ability to induce free radical oxidation reactions (Spiteller and Afzal, 2014), OM in sediments could also be strongly autoxidized.…”