Lecture 22 - Free radicals and antioxidants

Define antioxidants

Compounds that protect cells from damage caused by oxidation. Stabilise free radicals and repair damage.

What are some consequences of free radical damage in the body?

Cancer - free radical induced DNA mutations Athersclerosis Ageing-related damage Alcohol related liver damage Emphysema - free radicals in cigarette smoke Parkinson's, schizophrenia, Alzheimer's Haemochromatosis

Describe the mechanism of superoxide disumtase

Converts free radicals to less damaging substances such as hydrogen peroxide. Greatly accelerates removal of superoxide, which is directly toxic because it inactivates proteins with iron-sulphur centres

Which molecules in biological systems are prone to damage by free radicals?

DNA, proteins and PUFAs

Why would calorie restriction be associated with an increased lifespan?

Decreased metabolism results in decreased free radical production and therefore a decrease in oxidative damage.

Why are free radicals formed?

Environmental factors such as pollution, UV light, toxins, tobacco smoke, asbestos and radiation from x rays and gamma rays

What are some ways by which the body minimizes free radical damage/repair damage?

Enzymes such as superoxide dismutase, catalse, glutathione peroxidase and glutathione reductase, and vitamins A, C and E. In addition to this: polyphenol antioxidants, bilirubin and uric acid

What are free radicals?

Highly unstable atoms, molecules or complexes with one or more unpaired electrons, resulting from electron loss during oxidation. Free radicals are often uncharged and highly reactive.

Describe the general process that forms free radicals

Homolytic fission, or equal splitting of covalent bonds result in production of free radicals, because they produce a molecule or molecular fragment with an unpaired electron.

Describe the mechanism of free radicals

In ROS the oxygen molecule is capable of accepting an additional electron to create the superoxide anion, a more reactive form of oxygen. This is relatively unreactive alone but it can interact with NO to form peroxynitrile radical which is a potent oxidant of proteins and PUFAs, and can also break down hydroxyl radical and NO2. In addition to this, in the presence of transition metals superoxide anions can produce hydroxyl radicals via a 2-step sequence called Haber-Weiss and Fenton reactions. These can combine in the presence of poorly liganded iron (produced from haem breakdown and other iron-containing substances) in a catalytic cycle that produces the very damaging hydroxyl radical. Ie. free radical reactions can establish radical chains so that one radical can damage many biological molecules

Describe the mechanism of glutathione peroxidase

Removes hydrogen peroxide from the body and stops the production of free radicals in lipids

Describe the mechanism of catalse

Removes hydrogen peroxide from the body by converting it to water and oxygen. H2O2 is formed by superoxide dismutase

What is a reactive oxygen species (ROS)?

An oxygen molecule that becomes a free radical. Exist in liquid or gaseous state. Highly reactive with biological molecules.

How do antioxidants protect cells from oxidative damage?

Antioxidant vitamins: Donate H atoms to free radicals to stabilise them and reduce oxidative damage Antioxidant minerals: function within enzyme systems to convert free radicals to less damaging substances that can be excreted Antioxidant enzymes: break down oxidised fatty acids and make more vitamin antioxidants available to fight free radicals

What diseases are associated with ROS?

Asthma, arthritis, CVD, muscular dystrophy, Alzheimer's, Parkinson's, ALS, cancer (melanoma), diabetes, cataracts, kidney disease, accelerated ageing.

Describe transport of biological antioxidants

Biological antioxidants are readily absorbed and relatively non-toxic. They are transported to the relevant cellular site and inhibit oxidation of cellular components by decreasing localised oxygen concentration, scavenging free radicals, metabolising lipid peroxidesm chelating transition metal catalysts, and reacting with chain-propagating free radicals

How can free radicals be helpful in biological systems?

Kill bacteria by neutrophils and phagocytes, important in cell signalling and programmed cell death.

Why are free radicals harmful?

Oxidative stress damages biological membranes and cells, and free radicals are involved in disease processes. Damage occurs when exposure to free radicals exceeds the capacity of the antioxidant defence systems that counter free radicals.

How do antioxidants reduce cancer risk?

They enhance the immune system and inhibit cancerous cell growth and preventing oxidative damage to cells

Why are antioxidants important?

They protect biological systems against the potentially harmful effects of processes and reactions that cause excessive oxidation. They intercept radical chains by providing hydrogen atoms that are easily transferred, leading to stabilised radical products; they are chain terminating

What nutrients have antioxidant properties?

Vitamins E and C, carotenoids vitamin A (precursor beta carotene) Proteins: superoxide dismutase, catalase, glutathione peroxidase Phytochemicals: phytoestrogen, lycopene, flavenoids