1.4 Free Radical Injury

Question 1

Biochemical steps of free radical generation, and enzymes that eliminate them

Answer 1

O2 to .O2- to H2O2 to .OH- to H2O

.O2- (SOD)
H2O2 (Catalase)
.OH- (Glutathione Peroxidase)

Question 2

Causes of pathological generation of free radicals (4 categories)

Answer 2

1. Ionizing radiation
2. Inflammation–NADPH Oxidase for oxidative burst
3. Metals–Fe, copper
4. Drugs/chemicals–P450 metabolization generates free radicals

Question 3

Mech of free radical cell injury

Answer 3

• peroxidation of lipids

- oxidation of DNA/proteins

Question 4

Elimination of free radicals, how?

Answer 4

1. Antioxidants
2. Enzymes (SOD, Catalase, GP)
3. Metal carrier proteins (eg transferrin, ceruloplasmin)

Question 5

Examples of free radical injury

Answer 5

1. CCl4 toxicity

2. Reperfusion injury

Question 6

CCl4 toxicity

Answer 6

• ex of free radical injury
• Organic solvent in dry cleaning is converted to CCl4 by P450.
• Cell injury: cell swelling, RER ribosomes detach, protein synthesis decreases, decrease in apolipoproteins means cells keep fat. Eventually, fatty liver.

Question 7

Reperfusion injury

Answer 7

• Reperfusion results in free radical formation

- eg: continued rised in cardiac enzymes after reperfusion of MI