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7. MODULATION OF DNA DAMAGE (II) Conjugating enzymes, glutathione, antioxidant defences

  • Phase II reactions: various enzymes complete the biotransformation of toxic compounds started by the phase I enzymes. Typically, they conjugate the reactive oxidised intermediates to a carrier molecule, such as glutathione, GSH.

Defensive mechanisms have evolved that prevent oxidation by quenching or inactivation free radicals or reactive oxygen.

  • Glutathione is a very abundant sulphydryl-rich tripeptide. It is a powerful antioxidant, becoming oxidised by reactive oxygen to the dimer, GSSG. It is then regenerated, in a continuous cycle.

(See e-lecture Oxidative stress and vitamin E on glutathione and protective enzymes.)

  • Antioxidant enzymes



Enzymes:

  • Superoxide dismutase (SOD) - converts superoxide to hydrogen peroxide - contains copper and zinc

  • Catalase (breaks down hydrogen peroxide) - contains iron
  • Glutathione S transferase (GST) and GSH peroxidase (supports vitamin E in protection against lipid peroxidation) - contains selenium
  • (Thioredoxin reductase maintains antioxidant activity of vitamin C)

Dietary antioxidants may also play a role; see Other micronutrients electure .

http://meddev.uio.no/elaring/lcms13/ernaeringslaere/nutr-cancer-biology/illustrations/berries.jpg

Modulation of DNA damage

http://meddev.uio.no/elaring/lcms13/ernaeringslaere/nutr-cancer-biology/illustrations/water-tank.JPG

See Animation of Steady state equilibrium