Antioxidants, Cobalamin and Folic Acid

Antioxidants, Cobalamin and Folic Acid

Biological Oxidants:

-Oxygen, essential for life is also potentially toxic.

-98% of oxygen used by cells is reduced to harmless ground state oxygen or water.
-However, a small fraction of the oxygen in cells is converted to Active Oxygen (AO) species which can damage DNA, proteins, carbohydrates and lipids.

Free Radicals:

-An atom or group of atoms with an unpaired electron.

-Highly reactive.

-React with amino acids in proteins, lipids in membranes, bases in DNA.

-Products of these reactions generate other free radicals ---> chain reactions.

Active Oxygen Species (AO):

Singlet Oxygen:

Produced by UV Light

Though not really a "classic" free radical it is still very reactive. With two electrons singlet oxygen has an unstable conformation and is a great conributer to oxidative cellular damage.

Superoxide Radical Anion:

Though not a significant source of toxicity (short lived) it can be converted to hydrogen peroxide, peroxyl and hydroxyl radical.

Peroxyl Radical:

Hydroxyl Radical:

Produced from hydrogen peroxide, hydroxyl radical is the most reactive AO species causing damage to all four classes of biomolecules.

Lipid Peroxyl Radical:

When a free radical (R^. ) is formed it can react with a lipid to form a lipid radical, which in turn reacts with oxygen to form a lipid peroxyl radical (LOO^.).

Antioxidant Vitamins: C, E and carotenoids

Vitamin C:

Ascorbic acid itself can be oxidized to form a free radical which can act directly with AO species then proceed through a series of reactions to oxalic acid.

Deficiencies: scurvy

Toxicities: increased oxalic acid production -------> kidney stones

RDA: 60 mg

Vitamin E: a-tocopherol (major species)

a-Tocopherol can transfer a hydrogen atom to lipid peroxyl radical forming a stable species which is ultimately recycled back to vitamin E.

Deficiencies: rare, anemia, neurologic disorders

Toxicities: interferes with vitamin K metabolism -----> blood coagulation disorders

RDA: 10 mg

Carotenoids: Vitamin A

Very effective quenchers of singlet oxygen (1O2).

Deficiencies: so far not demonstrated

Toxicities: harmless yellowing of palms and soles of feet

RDA: 1,000 mg

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Hematopoietic Vitamins

Hematopoietic refers to RBC division and more specifically a lack of the "hematopoietic" vitamins results in reduced RBC division and anemia.

Folic Acid:

Required: for the synthesis of pyrimidines in DNA ----> RBC division

Function: carrier of one carbon units (i.e. methyl transfer reactions)

Source: nearly all foods.

Deficiencies: rare, impaired DNA biosynthesis ----> reduced RBC division ----> anemia.

RDA: 200 mg

Supplements: prescribed during pregnancy to reduce the incidence of neural tube defects in newborns.

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Cobalamin (B₁₂):

Required: for the synthesis of pyrimidines in DNA ----> RBC division.

Structure: complex molecule comprised of a metal (cobalt), a ring system and a nucleotide.

Function: carrier of one carbon units (i.e. methyl transfer reactions)

Source: must be synthesized by microorganisms, found in animal tissue or foods that have been bacterially fermented.

Deficiencies: rare, impaired DNA biosynthesis ----> reduced RBC division ----> anemia.

RDA: 2 mg