Lipid Peroxidation Biochemistry PDF

# Lipid Peroxidation Dr Shazia ## Mechanism of Lipid Oxidation - The overall mechanism of lipid oxidation consists of three phases: - **Initiation**: Fatty acid radical is produced. Initiators are reactive oxygen species (ROS), e.g. OH. Forms $H_2O$ + fatty acid radical - **Propagation**:...

# Lipid Peroxidation Dr Shazia ## Mechanism of Lipid Oxidation - The overall mechanism of lipid oxidation consists of three phases: - **Initiation**: Fatty acid radical is produced. Initiators are reactive oxygen species (ROS), e.g. OH. Forms $H_2O$ + fatty acid radical - **Propagation**: The fatty acid radical is unstable. It reacts readily with $O_2$ & creates a peroxyl-fatty acid radical. This is unstable. It reacts with another FFA. A different fatty acid radical is produced. Cycle continues. - **Termination**: Radical reaction stops when two radicals react and produce a non radical species. This happens when radical concentration is high. ## Initiation - Initiation is the step in which a fatty acid radical is produced. The most notable initiators in living cells are reactive oxygen species (ROS), such as OH (Hydroxyl radical) and $HO_2$ (hydroperoxyl radical) which combines with a hydrogen atom to make water and a fatty acid radical. **Image Description:** - A chemical diagram depicting the initiation process - The diagram shows an unsaturated lipid, hydroxyl radical, and water - The unsaturated Lipid reacts with the Hydroxyl radical and produces a water molecule and a lipid radical ## Propagation **Image Description:** - Chemical diagram depicting the propagation process - The diagram shows a lipid radical, oxygen molecule, and lipid peroxyl radical - The diagram also shows a lipid peroxide molecule. - The lipid radical reacts with the oxygen molecule to produce the lipid peroxyl radical. - The lipid peroxyl radical takes a hydrogen atom from a second lipid molecule to produce a lipid hydroperoxide and another lipid radical. ## Termination - When a radical reacts with a non-radical, it always produces another radical, which is why the process is called a "chain reaction mechanism". - The radical reaction stops when two radicals react and produce a non-radical species. ## Biomedical Importance - Responsible for - Rancidity (deterioration of foods) - Cancer - Inflammatory diseases - Atherosclerosis - Aging ## Antioxidants - Needed to control and reduce lipid peroxidation - Used as food additives. - Naturally occurring antioxidants are also present ### Antioxidants Used as Food Additives - Propyl gallate - Butylated hydroxyanisole (BHA) - Butylated hydroxytoluene (BHT) ### Naturally Occurring Antioxidants - Vitamin E (tocopherol) - Vitamin C - Urate - Beta-carotene ### Alpha Tocopherol (Vitamin E) - Alpha Tocopherol (Vitamin E) would intercept the peroxyl free radical and inactivate it before a PUFA can be attacked. - $T-OH + ROO' \rightarrow TO' + ROOH$ - The tocopheroxyl radical can react with another peroxyl radical getting converted to inactive products. - $TO' + ROO' \rightarrow$ inactive products - Vitamin E (Alpha tocopherol) acts as the most effective naturally occurring chain breaking antioxidant in tissues. - Only traces of tocopherol are required to protect considerable amounts of PUFA (1 tocopherol molecule per 1000 lipid molecules). - While acting as an antioxidant, alpha tocopherol is consumed. - Hence it has to be supplied on daily bases. - Vitamin E is the lipid phase antioxidant. - Vitamin C is the aqueous phase antioxidant. - Ceruloplasmin can act as an antioxidant in extracellular fluid. - Caffeine - Cysteine, glutathione - Vitamin A, beta-carotene - chain breaking but less effective than E - Other minor antioxidants are allopurinol, dimethyl thio urea, dimethyl sulfoxide. ### Antioxidants fall into two classes: - Preventive antioxidants - Chain-breaking antioxidants ## Preventive Antioxidants - Reduce the rate of chain initiation - Examples include: - Catalase - Glutathione peroxidase - Selenium - Chelators of metal ions (e.g. EDTA, DTPA) ## Chain-breaking Antioxidants - They interfere with chain propagation - They include: - Superoxide dismutase (acts in the aqueous phase) - Urate (acts in the lipid phase) - Vitamin E (acts in the lipid phase) ## Types of Antioxidant System - There are three main types of antioxidant systems: - Enzymes antioxidant system - Vitamins antioxidant system - Minerals antioxidant system ## Enzymes Antioxidant System - Enzymes antioxidant system has 3 enzymes: these enzymes destroy superoxide radical and hydrogen peroxide. - Superoxide dismutase (SOD) - Catalase - Glutathione peroxidase ### Superoxide dismutase (SOD) - Superoxide dismutase (SOD) catalyses the conversion of highly reactive superoxide radical ($O_2^-$) to relatively less toxic hydrogen peroxide. - $2H^+ + 2O2^- \xrightarrow{SOD} H_2O_2 + O_2$ ### Catalase - The role of catalase is to scavenge the $H_2O_2$ generated by superoxide dismutase - $2H_2O_2 \xrightarrow{Catalase} H_2O + O_2$ - Catalase decomposes hydrogen peroxide to water and oxygen. ## Vitamins Antioxidant System - Vitamins that has Antioxidant activity: - Tocopherol (Vitamin E) - B-carotenes (vitamin A). - Ascorbic acid (vitamin C) - Vitamin C, β-carotene, are also able to reduce and detoxify oxygen intermediates in cells. ## Minerals Antioxidant System - The activity of the antioxidant enzymes depends on supply of minerals: - Manganese - Copper - Zinc - Selenium - Manganese, copper, and zinc are required for the activity of superoxide dismutase. - Selenium is required for the activity of glutathione peroxidase. **Table Description**: - A table that highlights the reactive species and its corresponding antioxidant -Reactive Species | Antioxidant :---|:--- Superoxide free radical ($O_2^-$) and Hydroxyl free radical ($OH^*$) | Superoxide dismutase, Vitamin E, β-Carotene Hydrogen peroxide ($H_2O_2$) | Catalase, Glutathione, peroxidase Lipid peroxides ($LOO^*$) | Glutathione peroxidase Peroxy free radical ($ROO^*$) | Vitamin E and C