Reactive Oxygen Species

Question 1

Why is oxygen a double edged sword?

Answer 1

It’s necessary for ATP generation, detoxification and biosynthesis, but it can cause oxygen radical damage to lipids, proteins and DNA

Question 2

What makes a compound a free radical?

Answer 2

It’s a compound that contains a single unpaired electron in an orbital

and it’s capable of independent existense

Question 3

What do free radicals do in general?

Answer 3

they initiate chain reactions by extracting an electron from a neighboring molecule to complete their own orbitals

Question 4

Why are transition metals like Fe, Cu and Mo not considered free radicals?

Answer 4

they are relatively stable and don/t initiate chain reactions (plus they’re usually bound by proteins in the cell)

Question 5

Oxygen has two unpaired electrons in separate orbitals, so it’s called a…

Answer 5

biradical

Question 6

What does oxygen accept to become an ROS?

Answer 6

a single electron

Question 7

What are the three ROS species formed by the reduction of O2?

Answer 7

superoxide (1 electron added), the nonradical hydrogen peroxide, and the hydroxyl radical (3 electrons added)

Question 8

Where in the body is hydrogen peroxide naturally created enzymatically in the body?

Answer 8

peroxisomes (also mitochondria and ER)

Question 9

What are some things that can increase the formation of free radicals in cells?

Answer 9

drugs, natural UV radiation, pollutants, chemicals, smoking, etc.

Question 10

Superoxide anion is highly reactive, but why can’t it diffuse far?

Answer 10

it has limited lipid solubility

Question 11

What can superoxide form by reacting nonenzymatically in the Haber-Weiss reaction?

Answer 11

hydroxyl radical and hydroperoxy radicals

Question 12

What are some compounds that can cause nonenzymatic superoxide formation?

Answer 12

Coenzyme Q in the mirochondrial electron transport chain

cytochrome p450

NADPH oxidase (and pretty much any oxidase in the cell)

Question 13

Even though H2O2 is not actually a radical, why do we classify it as an ROS?

Answer 13

It can generate the hydroxyl radical, which is

Question 14

What catalyze the formation of the hydroxyl radical from H2O2?

Answer 14

transition metals like Fe2+ or Cu+ through the fenton reaction

Question 15

What do neutrophils turn hydrogen peroxide into during the respiratory burst to destroy invading organisms?

Answer 15

HOCl (hypochlorous acid)

Question 16

What radical is the most potent of the ROS?

Answer 16

the hydroxyl radical

Question 17

What two reactions will form hydroxyl radical? What are some other causes?

Answer 17

fenton reaction and haber-weiss reaction

also UV radiation

Question 18

What are some things the hydroxyl radical can damage?

Answer 18

Pretty much everything - lipids, proteins, DNA, etc

Question 19

RNOS are derived principally from what free radical?

Answer 19

NO

Question 20

How is NO formed endogenously?

Answer 20

through reactions of NO synthase

Question 21

What makes NO potentially more dangerous as a radical than, for example, superoxide?

Answer 21

It’s a gas so it can diffuse thorugh cytosol and lipid membranes into cells whereas superoxide is not lipid soluble

Question 22

At low levels, what does NO do?

Answer 22

acts as a neutrotransmitter and hormone that causes vasodilation

Question 23

What will NO do at HIGH concentrations?

Answer 23

It will combine with O2 to form additional reactive and toxic species and also cause vasoconstriction

Question 24

How do ROS damage membranes? What molecule in the urine/blood acts as an indicator of this?

Answer 24

They oxidize the lipids in the membrane, causing degradation

malondialdehyde is a byproduct of this - acts as a marker

Question 25

What do lpofuscin in cardiac cells, age spots, and lewy bodies have in common?

Answer 25

They are examples of signs of lipid peroxy radical damage

Question 26

What enzymes are used to form superoxide, HOCl and NO for normal immune function?

Answer 26

superoxide: NADPH oxidase
HOCl: myeloperoxidase
NO: nitric oxide synthase

Question 27

White blood cells undergo a rapid consumption of O2 to form ROS in order to break down invaders. What is the term for this?

Answer 27

respiratory burst

Question 28

What is chronic granulomatous disease a deficiency of?

Answer 28

NADPH oxidase

Question 29

What happens in chronic granulomatous disease?

Answer 29

It means they can’t form ROS appropriately for the immune system to function and end up developing infection after infection

Question 30

What is the inheritance pattern for chronic granulomatous disease?

Answer 30

x-linked recessive, so you see it mainly in boys

Question 31

Do boys with CGD tend to get more catalse-negative or catalase-positive infections? Why?

Answer 31

Catalase positive - catalase is capable of breaking down the small amount of hydrogen peroxide that the bacteria produces itself. so catalase negative bacteria will form enough hydrogen peroxide within the phagocytes to basically kill themselves.

Question 32

When are people usually diagnosed with CGD? Life expectancy?

Answer 32

Usually before age 5

92% now live beyond 8 years old and 50% live thorugh the third decade, but they typically die of infection

Question 33

What do you see on histology in a patient with chronic granulomatous disease?

Answer 33

giant cells and caseous necrosis

Question 34

What’s the treatment for chronic granulomatous disease?

Answer 34

vigilant surveillance, anti-microbial prophylaxis, gene therapy, bone marrow transplant, granulocyte transfusions

Question 35

In hypoxic cells that are rapidly reperfused, what can happen to cause damage?

Answer 35

Because of the reduced ATP, you have increased NA+ and Ca2+ levels. The reduced state of these carriers in the absence of O2 leads to increased superoxide production when oxygen becomes available during reperfusion, causing damage