FOM 3.2.3 Flashcards
What are some of the various ROS and RNS that participate in metabolism?
These are products that have an unpaired electron
How can NO be used as a signaling messenger? What are some current drugs that manipulate this?
NO is a quickly diffusing gas that is transient. It work in smooth muscle relaxation, vasodilation, and neurotransmission.
2 drugs currently utilze this:
Nitroglycerin - Creates more NO
Viagra - Allows that NO molecule to last longer
What are the 3 isoforms of Nitric oxide synthase and what is the reaction they catalyze?
endothelial NOS
inducible NOS
Neuronal NOS
They catalyze the reaction of L-arginine + 2O2 to L-citrulline + water and NO
Patient comes in that is hypertensive. Analysis of their endothelial cells shows a build-up of L-arginine. What could be a cause of this?
Mutation in the eNOS that does not function as properly thus leading to a buildup of L-Arginine. Pt would have lower amounts of NO leading to less vasodilation
Pt comes in and it hypotensive. They are shown to have a lot of NO in their system, what could be a cause of this?
Mutation in eNOS leading to an overactive enzyme. High amounts of NO could lead to increased vasodilation
What might cause an increase of Superoxide? How might this affect the function of the electron transport chain and can the increased intracellular act as a signaling molecule?
During a period of increased metabolic rate, the ETC can be referred to as “leaky”. It is not working at 100% efficiency and more electrons are falling off and generating superoxide. Cell can respond by increasing ADP present, Slowing the TCA cycle, or adding uncoupling transports that lower the amount of superoxide.
What is the role of reactive oxygen species in neutrophils? What properties of the bacteria make this even more effective?
Neutrophils use NADPH oxidase that creates superoxide from NADPH and uses it to destroy bacteria. The bacteria have unsequestered Iron which will then react with H2O2 created in a previous reaction and create products that are even more harmful to the bacteria.
In what way can ROS damage DNA and can you give an example?
ROS attack bases and backbones of nucleic acids.
Guanine can react with a ROS and create 8-hydroxylguanine that will pair with A instead of C
How can ROS affect amino acids?
ROS tend to attack amino acid residue with an “active” side chain such as cysteine, lysine, arginine, etc.
These can result in the formation of dityrosine bridges where two tyrosine side chains become covalently linked. The proteosome cannot degrade cross-linked proteins
How can ROS affect the plasma membrane?
It can break the chemical bonds of the FA compontent, an depleting the membrane of unsaturated fatty acids. This damages the fluidity of the membrane. Side note: it is said that fish oil and olive oil aid in this because they contain multiple double bonds that can stabilize the radical.
How do metal ions have role in the interconversion of ROS?
Iron catalyzes the formation of OH• and OH- from H2O2 (Fenton Rxn). These two are damaging to cellular components.
What are some enzymes that are used to control ROS?
Superoxide dismutase (makes up 1% of all proteins in cells)
Catalase (H2O2)
Glutathione peroxidase (H2O2)
Thioredoxin
What is the reaction that superoxide dismutase catalyzes?
two superoxide molecules react convert into hydrogen peroxide
What is the reaction catalase catalyzes?
What are some characteristics of non-enzymatic antioxidants? How can vitamin C be an example of this?
These tend to be reduced at baseline
Accept or donate electrons
Become radicals during the process
Less reactive that neutralized radical
Vitamin C uses resonance to stabilize the free electron
Answer is D - this is an example of unexpected chemistries that vitamins might have
