Oxidative Tissue Damage

Question 1

Oxidative Phosphorylation

Answer 1

reduction of O2 to water to produce ATP

Question 2

Cytochrome P450 pathway

Answer 2

metabolism of endogenous hormones and exogenous drugs/toxins

Question 3

Anti-microbial killing in phagocytes

Answer 3

NADPH oxidase, myeloperoxidase

Question 4

Importance of Oxygen

Answer 4

most abundant element on planet (47%), Ideal electron acceptor for biological catalysis

Question 5

O2 high redox potential can let it form ROS

Answer 5

Superoxide anion, hydrogen peroxide, hydroxyl radical (goes through these three radicals on the way to reduction to water)

Question 6

Endogenous source of ROS

Answer 6

oxidative phosphorylation, NADPH oxidases, peroxisomes, xanthine oxidase, free metals

Question 7

Environmental source of ROS

Answer 7

Cigarette smoke, radiation, drugs/pesticides, pollutants, ozone

Question 8

Mitochondrial electron leak

Answer 8

largest source of electron leak is ubiquinone; mito produce enzymes to fix leak (SOD I, II, III - take superoxide and metabolize it to hydrogen peroxide)

Question 9

Oxidative Stress

Answer 9

imbalance between oxidants and antioxidant defenses in favor of oxidants, leading to disruption of redox control/signaling and to cell and molecular damage

Question 10

Nitrostative Stress

Answer 10

RNS, products of NO syntheses, RNS interact with ROS to produce strong oxidants

Question 11

Oxidative tissue damage definition

Answer 11

chemical disruption of cellular/tissue structure and function by the oxidation of specific macromolecules

Question 12

Free Radical definition

Answer 12

a chemically-reactive atom or molecule with an unpaired or free electron

Question 13

Prevention of Oxidative Injury

Answer 13

control tissue pO2 to limit molecular oxidations; maintain basal and inducible anti-oxidant defense systems; sequester reactive transition metals (Fe, Cu) in unreactive forms

Question 14

Antioxidant Defenses

Answer 14

anti-oxidant enzymes; small molecule anti-oxidant defense; damage repair and disposal enzymes; transition metal sequestration

Question 15

Regulation of antioxidant enzymes

Answer 15

most anti-oxidant enzyme systems are both constitutive and inducible; increased expression relies on redox-sensitive kinases, phosphates, or TFs

Question 16

Antioxidant Enzymes…

Answer 16

content varies from tissue to tissue, but localizes to sites of ROS generation

Question 17

How do small molecule and dietary anti-oxidants work?

Answer 17

3 critical factors

1. bioavailability for reaction
2. local concentration of anti-oxidant molecule
3. kinetics of reaction

Question 18

Ascorbate Reaction

Answer 18

ascorbate donates an electron to quench a radical, resultant ascorbic radical is stabilized through resonance, additional oxidation then reduction

Question 19

Pulmonary Oxygen Toxicity

Answer 19

After exposure to 100% O2, there is an immediate increase in cellular ROS production; can lead to inflammation and destruction of lung; can cause fibrosis; intermittent exposure to high oxygen can promote tolerance of the toxic effect of high O2 by inducing anti-oxidant enzymes

Question 20

Ischemia-Reperfusion Injury

Answer 20

Oxidative tissue damage occurs primarily during the repercussion or re-oxygenation phase; during O2 deprivation, the stores of ATP, ADP, and AMP are depleted; causes xanthine to be converted to uric acid which produces hydrogen peroxide and superoxide; can react with metals to produce hydroxyl radicals which damage membranes

Question 21

Acute Inflammatory Response

Answer 21

Enzymes found in leukocytes (bleach and other chlorinating species) can leak from leukocytes and cause oxidative tissue damage during inflammation

Question 22

Cigarette smoking

Answer 22

smoke from tobacco contains more than 4,000 bioactive compounds; principal cause of COPD and lung cancer; depletes anti-oxidants by chronic stimulation of ROS/RNS production