Antioxidants and Their Enzymatic Mechanisms

• Antioxidants protect cells against the toxic effects of oxidative stress and contribute to disease prevention.
• They can be enzymatic or non-enzymatic, categorized as either endogenous or exogenous.
• Antioxidant mechanisms involve chain breaking or preventing chain reactions.

Enzymatic Antioxidants

• Enzymatic antioxidants work together to combat oxidative stress.
• Superoxide dismutase (SOD) is a key enzyme.
• Catalase is another important enzymatic antioxidant.
• Glutathione peroxidase and glutathione reductase work in conjunction.

Superoxide Dismutase (SOD)

• SOD converts superoxide into hydrogen peroxide (H2O2).
• SOD acts as the first line of defense against oxidative stress.
• Superoxide (O2-) is a strong initiator of chain reactions.
• SOD exists in different isoforms: SOD1 (Cu+/Zn2+) found in the cytosol, SOD2 (Mn2+) in mitochondria, and SOD3 (Cu+/Zn2+) in the extracellular space.

Catalase

• Catalase reduces hydrogen peroxide (H2O2) into water (H2O).
• It prevents hydroxyl radical formation in Fenton or Haber-Weiss reactions.
• Catalase is principally located in peroxisomes.
• The highest catalase activity is found in the liver and kidney.

Glutathione Peroxidase

• Glutathione peroxidase is a selenium enzyme.
• It reduces hydrogen peroxide (H2O2) to water (H2O).
• This enzyme is present in high concentrations in mitochondria alongside glutathione.
• It prevents lipid peroxidation.

Non-Enzymatic Antioxidants

• Non-enzymatic antioxidants act as free radical scavengers.
• They can be endogenous or exogenous.

Endogenous Antioxidants

• Endogenous antioxidants include lipoid acid.
• Glutathione is an endogenous antioxidant.
• L-arginine is also an endogenous antioxidant.
• Coenzyme Q10 is a notable endogenous antioxidant.
• Melatonin is produced in the pineal gland from tryptophan and acts as a free radical scavenger.
• Uric acid is also an endogenous antioxidant.
• Bilirubin acts as an endogenous antioxidant.
• Metal-chelating proteins are part of the endogenous antioxidant system.

Melatonin

• Melatonin donates an electron to neutralize free radicals.
• It reacts with reactive oxygen species (ROS) and reactive nitrogen species (RNS).
• Melatonin has both hydrophilic and hydrophobic properties.
• It can pass through membranes and the blood-brain barrier.

Exogenous Antioxidants

• Exogenous antioxidants assist endogenous antioxidants.
• They require a continuous supply through diet.
• Deficiencies in these antioxidants can lead to diseases.
• Key exogenous antioxidants include vitamins E and C, carotenoids, trace metals like selenium, manganese, and zinc, as well as flavonoids.

Vitamin E

• Vitamin E has eight stereoisomers.
• Alpha-tocopherol is the most bioactive form in humans.
• It is lipid-soluble and protects against lipid peroxidation in membranes.
• Vitamin E efficiently terminates chain reactions during lipid peroxidation.
• It donates single electrons to peroxyl radicals (LOO) to form stable lipid peroxide (LOOH).
• Vitamin E reduces the incidence of chronic diseases.
• Cooking and storage can destroy a-tocopherol in foods.

Vitamin C (Ascorbic Acid)

• Vitamin C is water-soluble.
• It is involved in collagen, carnitine, and neurotransmitter biosynthesis.
• Vitamin C works synergistically with vitamin E to quench free radicals.
• Its principal role is the regeneration of the reduced form of vitamin E.
• Vitamin C is anti-atherogenic, anti-carcinogenic, and acts as an immunomodulator.
• It reduces the incidence of cardiovascular diseases (CVD) and some cancers.
• Vitamin C is heat labile and can be lost during cooking.

Urate

• Urate is a potent antioxidant.
• It removes singlet oxygen, hydroxyl radicals, hydroxyl peroxide, and peroxynitrite.
• Urate is particularly important for preventing oxidative damage in the human brain.
• Oxidative stress may be one of the causes of the loss and degeneration of dopaminergic neurons in the substantia nigra of Parkinson's Disease (PD).

Beta-Carotene

• Beta-carotene is a lipid-soluble member of the carotenoid family.
• It acts as a precursor for vitamin A, which can be converted to retinol.
• Beta-carotene is a strong antioxidant and the best quencher of singlet oxygen.

Flavonoids

• Flavonoids are polyphenolic compounds present in plants.
• They exhibit potent antioxidant activity.
• Some flavonoids can inhibit enzymes responsible for superoxide production, such as xanthine oxidase.
• Others efficiently chelate iron (Fe) and copper (Cu).
• Flavonoids act as free radical scavengers by donating electrons to superoxide or lipid peroxy radicals.
• They can reduce the incidence of chronic and degenerative diseases.
• Every plant contains a unique combination of flavonoids.

Selenium

• Selenium (Se) is a trace mineral found in soil, water, and vegetables.
• It is an active site of several antioxidant enzymes, including glutathione peroxidase.
• Selenium is an antioxidant, anti-carcinogenic, and immunomodulator.
• It is also necessary for thyroid function.