Free Radicals & Antioxidant Nutrient

Free radicals

Highly reactive molecules with an unpaired electron that try to steal electrons from other molecules, creating a chain reaction.

Superoxide (•O₂⁻), Hydroxyl (•OH), Perhydroxyl (•O₂H).

Great examples of damaging oxygen radicals (ROS)

Termination of free radical chain reaction

What happens when two free radicals meet and pair their electrons, stabilizing each other.

How free radicals damage DNA

They alter nitrogenous bases, causing mutations that may lead to cancer if not repaired.

Lipid peroxidation

Process where free radicals target unsaturated fatty acids in membranes, forming lipid peroxides → leads to membrane instability and cell death.

Modification of proteins by free radicals

They modify tyrosine residues, forming dihydroxyphenylalanine (DOPA), which can generate more radicals.

FOX assay

A test that measures lipid peroxides through the oxidation of Fe²⁺ to Fe³⁺.

TBARS assay

A test that measures reactive aldehydes produced by lipid peroxidation.

Pentane (n-6) and ethane (n-3).

What hydrocarbons exhaled after lipid peroxidation n-6 and n-3 fatty acids

Antioxidants

Their role is to neutralize free radicals by donating electrons without becoming unstable themselves.

cancer

the result of DNA damage in somatic cells can cause mutations → uncontrolled cell growth

Atherosclerosis

this results when radicals modify LDL → not recognized by LDL receptors → uptake by macrophages → foam cells → plaque formation.

nitric oxide (NO)

this reacts with superoxide to form peroxynitrite, which decays into hydroxyl radicals leading to radical formation

NADPH oxidase.

Main enzyme in respiratory burst of macrophages

autoimmune disease

the result when modified proteins are recognized as foreign → antibodies attack both modified and normal proteins.

Fenton reaction

Fe²⁺ + H₂O₂ → Fe³⁺ + •OH + OH⁻.

About 1.5 mol

How much ROS generated daily from mitochondrial respiration

TBARS assay (Thiobarbituric Acid Reactive Substances).

a test for lipid peroxidation products

Metal ions like iron and copper are bound to proteins like transferrin, ferritin, ceruloplasmin, and metallothionein to prevent ROS formation.

How do metal ions prevent ROS formation?

Superoxide dismutase (SOD)

Enzyme converting superoxide to hydrogen peroxide

Catalase and peroxidases.

Enzymes removing hydrogen peroxide

glutathione peroxidase

this enzyme reduces lipid peroxides to hydroxy fatty acids using glutathione (GSH).

Vitamin C (Ascorbate).

Vitamin regenerating tocopheroxyl radical

Ascorbate, uric acid, and polyphenols.

Examples of water-soluble radical-trapping antioxidants

Vitamin E, ubiquinone, and carotenes.

Examples of lipid-soluble radical-trapping antioxidants

Selenium

This element is required for the activity of glutathione peroxidase.

perixosomes

Location of SOD and catalase enzymes

It uses NADPH to reduce glutathione disulfide (GSSG) to reduced glutathione (GSH)

how does glutathione reductase regenerate glutathione

It reaches the renal threshold and is excreted in the urine

what happens when ascorbate concentration exceeds 30 mmol/L in plasma?

because at high oxygen pressures (like in the lungs), β-carotene becomes a pro-oxidant and initiates radical damage

Why can β-carotene increase lung cancer risk despite being an antioxidant?

The stable vitamin E radical persists long enough to penetrate deeper into lipoproteins and cause oxidative damage.

How does vitamin E become a pro-oxidant in plasma lipoproteins?

because they can quench signaling radicals (like nitric oxide), allowing damaged cells to survive and increasing cancer risk.

how high levels of antioxidants can be a cancer risk

nitric oxide (NO)

Radical important for apoptosis signaling