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Lipid peroxidation, or lipid oxidation, is a complex chemical process that leads to oxidative degradation of lipids, [1] resulting in the formation of peroxide and hydroperoxide derivatives. [2] It occurs when free radicals , specifically reactive oxygen species (ROS), interact with lipids within cell membranes , typically polyunsaturated fatty ...
The antioxidant enzyme glutathione peroxidase 4 (GPX4) belongs to the family of glutathione peroxidases, which consists of 8 known mammalian isoenzymes (GPX1–8).GPX4 catalyzes the reduction of hydrogen peroxide, organic hydroperoxides, and lipid peroxides at the expense of reduced glutathione and functions in the protection of cells against oxidative stress.
Ferroptosis can be inhibited by lipophilic radical trapping antioxidants such as ferrostatin-1, [1] [3] liproxstatin-1, [3] and vitamin E. [30] Chelation of iron by agents such as desferrioxamine mesylate (DFO) also prevents lipid peroxidation and suppresses ferroptosis. [31] [109]
Glutathione peroxidase 4 (GPx4) has a high preference for lipid hydroperoxides; it is expressed in nearly every mammalian cell, though at much lower levels. Glutathione peroxidase 2 is an intestinal and extracellular enzyme, while glutathione peroxidase 3 is extracellular, especially abundant in plasma. [ 4 ]
The deuterium-reinforced lipids resists the non-enzymatic lipid peroxidation (LPO) through isotope effect — a non-antioxidant based mechanism that protects mitochondrial, neuronal and other lipid membranes, thereby greatly reducing the levels of numerous LPO-derived toxic products such as reactive carbonyls. [4] [5]
Deuterium-reinforced lipids can be used for protecting living cells by slowing the chain reaction of lipid peroxidation. [1] The lipid bilayer of the cell and organelle membranes contain polyunsaturated fatty acids (PUFA) are key components of cell and organelle membranes. Any process that either increases oxidation of PUFAs or hinders their ...
Alpha-tocopherol is a fat-soluble antioxidant functioning within the glutathione peroxidase pathway, [15] and protecting cell membranes from oxidation by reacting with lipid radicals produced in the lipid peroxidation chain reaction. [3] [16] This removes the free radical intermediates and prevents the oxidation reaction from continuing.
Assay of TBARS measures malondialdehyde (MDA) present in the sample, as well as malondialdehyde generated from lipid hydroperoxides by the hydrolytic conditions of the reaction. [4] MDA is one of several low-molecular-weight end products formed via the decomposition of certain primary and secondary lipid peroxidation products.