Antioxidants

Question 1

Reactive Oxygen Species

(ROS)

Production

Answer 1

ROS are by-products of oxygen metabolism.

Typically generated in the mitochondria.

• Add 1 e^- ⇒ superoxide (O₂^-)
• Add 2 e^- ⇒ hydrogen peroxide (H₂O₂)
• Add 3 e^- ⇒ extremely reactive hydroxyl radical (OH・)
• Concerted addition of 4 electrons generates the desired H₂O product

Nitric oxide (NO・) is another physiological free radical.

Question 2

Effects of ROS

Answer 2

• In membranes and lipoproteins, hydroxyl radical acts on unsaturated fatty acid groups to form lipid carbon-centered radicals
  
  • Can initiate a chain reaction
  • Lipid carbon-centered radicals seen as foreign
• Oxidative stress occurs when production of ROS faster than antioxidant defenses can consume them
  
  • Ex. respiratory burst
  • Can lead to cell damage and death
• With ischemia-reperfusion injury, most tissue damage occurs on re-exposure to oxygen
  
  • Tissue undergoes necrosis and death

Question 3

ROS Associated Diseases

Answer 3

• Cancer development through oxidative DNA damage leading to mutagenesis
• Atherosclerosis due to oxidation of LDL and uptake by macrophages ⇒ foam cells
• Alzheimer’s disease due to neuronal death from elevated NO and/or mitochondrial dysfunction
• Aging attributed to progressive decline in mitochondrial function

Question 4

Vitamin E

Sources and Absorption

Answer 4

Lipophilic Antioxidant

• Synthesized in plants
  
  • High levels in grains and vegetable oils
  • wheat germ, whole grain bread and cereals, egg yoke, nuts and sunflower seeds
• Absorbed in intestines and transported to liver in chylomicrons
• May include a variety of tocopherols (saturated side-chains) and tocotrienols (3 double bonds in side-chain)
  
  • 𝛼-tocopherol with highest activity ⇒ “natural” vitamin E
• RDA is 15 mg/day
• TUL is 1,000 mg/day
  
  • Vit E supplementation at high doses can compete with Vit K

Question 5

Vitamin E

Functions

Answer 5

Lipophilic Antioxidant

• Can function as a chain-breaking antioxidant
• Prevents propagation of lipid carbon-centered radicals of FA residues of membranes
• Able to cross BBB and protect lipids in CNS from oxidative damage
  
  • Deficiency can result in neurological sx
• Important at blocking formation of atherogenic lipoprotein species
  
  • Concomitant reduction in CAD not yet adequately demonstrated
• Antioxidant supplements are not currently recommended

Question 6

Vit E Deficiency

in

Celiac Disease

Answer 6

Celiac’s results in autoimmune damage of intestinal villous.

Prevents absorption of lipid-containing mixed micelles which would normally deliver fat-soluble vitamins to enterocytes.

Results in malabsorption of many nutrients including iron, calcium, Vit D, and less frequently Vit E.

Causes progressive systemic degeneration of large-caliber myelinated sensory axons in spinal cord and peripheral nerves.

Presenting symptoms:

Neuromyopathy, Sensory neuropathy, Optic atrophy, Cerebellar syndrome

Hemolytic anemia, myopathy, weakness, ataxia, impaired reflexes, ophthalmoplegia, retinopathy, damage to nervous tissue

Treatment includes Vit E replacement with 𝛼-tocopherol.

Question 7

Vitamin C

Answer 7

Major hydrophilic antioxidant vitamin.

Many important physiological roles:

1. Returns Vit E back to reduced state
   
   • Indirectly impacts oxidation of membrane components
2. Important for collagen synthesis
   
   • Coenzyme for several hydroxylases
   • Vit C deficiency results in scurvy
     
     • loose teeth, bleeding gums, ecchymoses, slow wound healing
3. Dietary Vit C reduces ferric iron to ferrous iron (absorbed form)
   
   • Results in improved absorption of dietary iron

Beneficial effects of ascorbate seen in lowered markers of DNA oxidation (8-oxoguanine) and lowered markers for membrane oxidation (malondialdehyde)

Question 8

Antioxidant Enzymes

Answer 8

ROS are enzymatically inactivated.

• Superoxide dismutase
  
  • superoxide → hydrogen peroxide
  • mammals with at least 2 isozymes
• Catalase
  
  • hydrogen peroxide → water and oxygen
  • heme protein
  • located in peroxisomes
• Glutathione peroxidases
  
  • Catalyzes reduction of H₂O₂ by glutathione (GSH)
  • Oxidized GSSG returned to GSH by glutathione reductase utilizing NADPH
  • Found in cytosol
  • Selenium is an important prosthetic group in these enzymes and is therefore essential.

Question 9

Flavonoids & Flavones

Answer 9

Plant-derived hydrophilic antioxidants.

Found in blueberries, green tea, red wine, and cocoa.

Possible role in reduction of CAD and cancer.

Question 10

Carotenoids

Answer 10

Have also been suggested to act as antioxidants.

Ex. beta-carotene

Question 11

Antioxidant Supplementation

Answer 11

Studies unable to prove health benefits of antioxidant supplements.

Balanced diet rather than supplementation is the most consistent health recommendation.

Many antioxidants advertised without significant scientific validation e.g. lipoic acid, CoQ, grape seed extract.