Reactive Oxygen Species Flashcards
Why is oxygen a double edged sword?
It’s necessary for ATP generation, detoxification and biosynthesis, but it can cause oxygen radical damage to lipids, proteins and DNA
What makes a compound a free radical?
It’s a compound that contains a single unpaired electron in an orbital
and it’s capable of independent existense
What do free radicals do in general?
they initiate chain reactions by extracting an electron from a neighboring molecule to complete their own orbitals
Why are transition metals like Fe, Cu and Mo not considered free radicals?
they are relatively stable and don/t initiate chain reactions (plus they’re usually bound by proteins in the cell)
Oxygen has two unpaired electrons in separate orbitals, so it’s called a…
biradical
What does oxygen accept to become an ROS?
a single electron
What are the three ROS species formed by the reduction of O2?
superoxide (1 electron added), the nonradical hydrogen peroxide, and the hydroxyl radical (3 electrons added)
Where in the body is hydrogen peroxide naturally created enzymatically in the body?
peroxisomes (also mitochondria and ER)
What are some things that can increase the formation of free radicals in cells?
drugs, natural UV radiation, pollutants, chemicals, smoking, etc.
Superoxide anion is highly reactive, but why can’t it diffuse far?
it has limited lipid solubility
What can superoxide form by reacting nonenzymatically in the Haber-Weiss reaction?
hydroxyl radical and hydroperoxy radicals
What are some compounds that can cause nonenzymatic superoxide formation?
Coenzyme Q in the mirochondrial electron transport chain
cytochrome p450
NADPH oxidase (and pretty much any oxidase in the cell)
Even though H2O2 is not actually a radical, why do we classify it as an ROS?
It can generate the hydroxyl radical, which is
What catalyze the formation of the hydroxyl radical from H2O2?
transition metals like Fe2+ or Cu+ through the fenton reaction
What do neutrophils turn hydrogen peroxide into during the respiratory burst to destroy invading organisms?
HOCl (hypochlorous acid)
What radical is the most potent of the ROS?
the hydroxyl radical
What two reactions will form hydroxyl radical? What are some other causes?
fenton reaction and haber-weiss reaction
also UV radiation
What are some things the hydroxyl radical can damage?
Pretty much everything - lipids, proteins, DNA, etc
RNOS are derived principally from what free radical?
NO
How is NO formed endogenously?
through reactions of NO synthase
What makes NO potentially more dangerous as a radical than, for example, superoxide?
It’s a gas so it can diffuse thorugh cytosol and lipid membranes into cells whereas superoxide is not lipid soluble
At low levels, what does NO do?
acts as a neutrotransmitter and hormone that causes vasodilation
What will NO do at HIGH concentrations?
It will combine with O2 to form additional reactive and toxic species and also cause vasoconstriction
How do ROS damage membranes? What molecule in the urine/blood acts as an indicator of this?
They oxidize the lipids in the membrane, causing degradation
malondialdehyde is a byproduct of this - acts as a marker
What do lpofuscin in cardiac cells, age spots, and lewy bodies have in common?
They are examples of signs of lipid peroxy radical damage
What enzymes are used to form superoxide, HOCl and NO for normal immune function?
superoxide: NADPH oxidase
HOCl: myeloperoxidase
NO: nitric oxide synthase
White blood cells undergo a rapid consumption of O2 to form ROS in order to break down invaders. What is the term for this?
respiratory burst
What is chronic granulomatous disease a deficiency of?
NADPH oxidase
What happens in chronic granulomatous disease?
It means they can’t form ROS appropriately for the immune system to function and end up developing infection after infection
What is the inheritance pattern for chronic granulomatous disease?
x-linked recessive, so you see it mainly in boys
Do boys with CGD tend to get more catalse-negative or catalase-positive infections? Why?
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.
When are people usually diagnosed with CGD? Life expectancy?
Usually before age 5
92% now live beyond 8 years old and 50% live thorugh the third decade, but they typically die of infection
What do you see on histology in a patient with chronic granulomatous disease?
giant cells and caseous necrosis
What’s the treatment for chronic granulomatous disease?
vigilant surveillance, anti-microbial prophylaxis, gene therapy, bone marrow transplant, granulocyte transfusions
In hypoxic cells that are rapidly reperfused, what can happen to cause damage?
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
