Mechanism of toxicity pt 2

Question 1

what are the two types of reactive metabolites?

Answer 1

Electrophiles - most common, have an electron-deficient atom i.e. they have + charge
Nucleophiles - has an electron-rich atom, less common

Question 2

what are Electrophiles produced by?

Answer 2

• Oxidative stress/metabolism (p450)
• peroxides’
• Alcohol dehydrogenase

Question 3

Name the Reactive Oxygen species (ROS)

Answer 3

oxygen radicals:

• superoxide anion radical
• hydroxyl radical
• non-radicals hydrogen peroxide H2O2

Question 4

which one of the following cause oxidative stress :
A - superoxide anion radical 
B - hydroxyl radical
C - non-radicals hydrogen peroxide H2O2
D - ALL OF THE ABOVE

Answer 4

D - ALL OF THE ABOVE

Question 5

what is oxidative stress?

Answer 5

an imbalance between free radicals and antioxidants in the body

Question 6

how can free radicals be formed?

Answer 6

• can be formed by the loss of a single electron from a non-radical
• or by the gain of a single electron by a non-radical

Question 7

oxygen is usually reduced to what in biological systems?

Answer 7

water

Question 8

name the physiological pathways that CATALYZE REDUCTION of oxygen to water

Answer 8

• cytochrome p450s

- mitochondrial electron transport chain

Question 9

xenobiotics can accept electrons from

Answer 9

• electron transport chain
• NADPH via reductase enzyme

(Both reduced xenobiotics can donate free electrons to oxygen to produce more ROS)

Question 10

what is redox cycling?

Answer 10

a chemical reaction between two substances in which one substance is oxidized and the other reduced.

Question 11

How is SUPEROXIDE detoxified?

Answer 11

by hydrogen peroxide by superoxide dismutase

Question 12

how is HYDROGEN PEROXIDE detoxified?

Answer 12

by catalase or glutathione peroxide

Question 13

how is HYDROXYL RADICAL detoxified?

Answer 13

only produced if hydrogen peroxide is NOT detoxified