40-OXIDANT DAMAGE AND ITS PREVENTION – Dr. Groseclose Flashcards
Name the 4 chemical species derived by progressive reduction of molecular oxygen.
O2 + e- –> O2- [superoxide anion] O2 + 4e- + 4H+ –> 2H2O [water]
O2 + 2e- + 2H+ –> H2O2 [hydrogen peroxide]
O2 + 3e- + 3H+ –> H2O + HO(dot) [hydroxyl radical]
How are oxidant species generated in vivo?
The electrons come from reduced species such as NADPH, NADH and FADH.
How are the biological molecules damaged by oxidant species?
Proteins – inactivated or made more susceptible to proteolysis by having cysteine-SH groups oxidized, tryptophan destroyed, tyorisine & methionine modified, and the main chain/peptide bonds broken.
Polysaccharides – oxidants depolymerize mucins and Hyaluronic acid, destroying flow and lubricant properties. [synovial fluid]
Nucleic Acids – are depolymerized which may alter the genetic message. Effects Mitochondrial DNA more b/c lack of histones and proximity to source of oxidants.
Lipids – are peroxidized, leading to changes in membrane fluidity and permeability
Name the 5 antioxidant enzymes. Name 3 biological antioxidants that are not enzymes.
Antioxidant enzymes:
- Superoxidase dismutase
- Glutathione reductase
- Catalase
- Methionine sulfoxide reductase
- Glutathione peroxidase
Biological Antioxidants
- Vitamin C
- Glutathione
- Vitamin E
Discuss the beneficial aspects of oxidants in biological systems.
- Ozone (O^3) protects from radiant damage.
- Phagocytic cells kill pathogens with oxidants.
- Routine oxidations are important in metabolism: Nitric oxide (vasodilation), thyroid hormone synthesis, P450 systems, collagen cross linking
- Tryptophan oxygenase: Aromatic AA metabolism
Therapeutic uses of oxidants
- Billirubin light for neonatal jaundice
- PUVA therapy for psoriasis
- Benzoyl peroxide for acne
- Radiation therapy
- Photfrin as a photosensitizer for tumor tissue
Define and discuss:
- chronic granulomatous disease
- acatalasemia
- glucose 6 – phosphate dh deficiency
Chronic granulomatous disease (GCD) – NADPH oxidase is defective. Patients suffer multiple infections because macrophages cannot kill microbes after they are phagocytosed. This is a serious disease can lead to baby death by infection.
Acatalasemia – complete absence of catalase has been reported in families in Japan. Only apparent abnormality in these people is an increased incidence of periodontal infections. Not a serious disease. Oral ulcerations and gangrene may be present.
Glucose 6–Phosphate Dehydrogenase deficiency – a very common usually clinically silent, disease that leads to production of reduced Oxygen species at the expense of NADPH stores. Leads to MASSIVE hemolysis (fatal)
Name the chlorine-containing oxidant produced by activated macrophages.
Activated macrophages produce ClO4- (bleach) via myloperoxidase.
Name the nitrogen-centered radical formed by the reaction of nitric oxide with superoxide.
perooxynitrite (ONOO^-)
So bad!
- Discuss the role of oxidant species and oxidative damage in the pathological process of
atherosclerosis, chronic inflammation, ischemia/reperfusion, etc.
- Arthritis/chronic inflammation: can occur due to depolymerization of hylauranic acid (a polysaccharide) that will no longer be able to lubricate joints.
- Ischemia/Reperfusion: Ischemia helps convert xanthine dehydrogenase to xanthine oxidase that transfers e- to O2 instead of NAD+. When O2 made available again (during reperfusion), O2 is reduced to O2- and H2O2.
- Atherosclerosis: LDL becomes oxidized and then interacts with receptors in the phagocytic cells of arterial wall.
- LDL –> LDL-oxidized –> foam cells
- Aging: Many of the changes associated with aging are considered to be cumulative effects of oxidant damage to connective tissue, oxidants released during chronic inflammatory responses and somatic mutations due to oxidant damage to DNA.
- Discuss the concept of “redox balance” and the
ways in which it plays a role in the
normal activity of cells and tissues.
…
