domingo, 22 de diciembre de 2019

Antioxidant Metabolites

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By Dr. Ananya Mandal, MDReviewed by April Cashin-Garbutt, MA (Editor)

The antioxidant networks in the body are complex and are composed of several components. These may be endogenous factors such as Glutathione, thiols, haem proteins, Coenzymes Q, bilirubin and urates. These may also be endogenous enzymes like GSH reductase, GSH transferase, GSH peroxidises, Superoxide dismutase and Catalases.

Dietary factors

Some nutritional and dietary factors also function as antioxidant metabolites or parts of the antioxidant metabolic pathways. These include Ascorbic acid or vitamin C, Tocopherols or vitamin E, beta carotenes and retinoids, Selenium, Methionine etc.

Antioxidant metabolite	Solubility	Concentration in human serum (μM)	Concentration in liver tissue (μmol/kg)
Ascorbic acid (vitamin C)	Water	50 – 60	260 (human)
Glutathione	Water	4	6,400 (human)
Uric acid	Water	200 – 400	1,600 (human)retinol (vitamin A): 1 – 3
α-Tocopherol (vitamin E)	Lipid	10 – 40	200 (human)

Classification of antioxidant metabolites

Antioxidant metabolites are further classified as soluble in water (hydrophilic) or in lipids (hydrophobic). Water-soluble antioxidants react with oxidants in the cell cytosol and the blood plasma. On the other hand lipid-soluble antioxidants protect cell membranes from lipid peroxidation.

The actions of each of these metabolites are dependent on each other as the metabolic pathways are complex. Selenium and zinc are commonly referred to as ''antioxidant nutrients''. These alone do not have antioxidant properties but are required for the activity of some antioxidant enzymes.

Vitamin C or Ascorbic acid

This is a monosaccharide antioxidant found in both animals and plants. This is one of the essential nutrients for living organisms like humans. It must be obtained from the diet of humans and is a vitamin. Most other animals are able to produce this compound in their bodies and do not require it in their diets.

The vitamin is maintained in its reduced form by reaction with glutathione within the cell. It can be catalysed by protein disulfide isomerase and glutaredoxins.

Since it exists as a reduced agent, it can neutralize reactive oxygen species such as hydrogen peroxide. Ascorbic acid also is a substrate for the antioxidant enzyme ascorbate peroxidise. This is important for preventing oxidative stress particularly in plants.

Vitamin E or tocopherols

Vitamin E includes around eight related tocopherols and tocotrienols. These are fat-soluble vitamins with antioxidant properties.

Of these, alpha tocopherol is the most studied component as it has the highest bioavailability. The body absorbs this vitamin along with fats. It has been claimed that the α-tocopherol form is the most important lipid-soluble antioxidant. This vitamin protects membranes from oxidation by reacting with lipid radicals produced in the lipid peroxidation chain reaction. The reaction removes free radical intermediates and prevents the propagation reaction.

Once completed the oxidised α-tocopheroxyl radicals can be recycled back to the active reduced form through reduction by other antioxidants, such as ascorbate, retinol or ubiquinol. This α-tocopherol protects glutathione peroxidase 4 (GPX4)-deficient cells from cell death.

Glutathione

This is an endogenous antioxidant factor. Glutathione contains cysteine and is a peptide found in most forms of aerobic life. It is not required in the diet and is instead synthesized in cells from its constituent amino acids.

Glutathione contains a thiol group in its cysteine moiety which is a reducing agent and can be reversibly oxidized and reduced. In cells, glutathione is maintained in the reduced form by the enzyme glutathione reductase. This reduced glutathione reduces other metabolites and enzyme systems, such as ascorbate in the glutathione-ascorbate cycle, glutathione peroxidases and glutaredoxins.