Oxidative Damage

Question 1

Characterize the different reactive oxygen species (ROS) and explain the physiological sources of ROS

Answer 1

superoxide is O2-, it’s mildly reactive, and is formed in mitochondria by picking up an electron from CoQ in the electron transport chain

H2O2 is hydrogen peroxide, it’s not very reactive, and is formed from superoxide by the enzyme superoxide dismutase or as a byproduct in other metabolic reactions like fatty acid oxidation

hdroxy radical is OH-, it’s formed by the Fenton rxn which turns H2O2 to HO- and HOrad. The rxn requires Fe2+ which is generated from Fe3+ and (superoxide or vitC)

Question 2

Describe the types of damage that ROS cause, including the mechanism by which lipids are damaged, and the known and presumed disease consequences of different types of oxidative damage

Answer 2

it causes lipid oxidation, specifically through a radical chain reaction in which a lipid radical propagates other lipid radicals

radicalization of guanine is especially potent in DNA damage

it’s presumed that genetic defects in superoxide dismutase can cause familial amyotrophic lateral sclerosis

also can cause reactive nitrogen oxide species like peroxynitrite

radical damage of lipids is thought to cause atherosclerotic plaques

Question 3

Know the enzymes that protect against and repair oxidative damage, and understand precisely how they work.

Answer 3

superoxide dismutase turns superoxide into hydrogen peroxide, it has many isoforms and usually requires copper or zinc as cofactors

glutathione peroxidase reduces H2O2 to water

Question 4

Understand the roles of small molecules, including ascorbic acid, tocopherol, glutathione, and uric acid, in defense against oxidative damage.

Answer 4

they act as relatively stable free radicals so they terminate radical reactions