BSI Lecture 39-40 Free Radicals and Antioxidants Flashcards
What is another name for free radicals?
Reactive Oxygen Species (ROS) or Reactive Nitrogen Species (RNS)
What is a free radical?
An atom or molecule with an unpaired electron.
T or F? Free radicals are very reactive with other molecules.
True
What is the name of O2 (superscript dot)?
Superoxide
What is the name of HO (superscript dot)?
Hydroxyl radical
What is the name of NO (superscript dot)?
Nitric Oxide
What are the ROS/RNS that are technically not free radical?
Hydrogen peroxide (H2O2) and Peroxynitrite (ONOO-)
What do ROS/RNS do?
- Act as signaling molecules
2. Damage other molecules (i.e proteins, lipids, nucleic acids)
How do ROS/RNS react with other molecules?
- Attach itself to another molecule
- Act as an oxidizing agent
- Act as reducing agents
Where in the cells are ROS/RNS produced?
Mitochondria
T or F? ROS/RNS are produced only in certain cells.
False, they are produced in all cells of the body during aerobic respiration
Single electrons “leak” from complexes ___ and ____ of the ETC and attach to O2 to form superoxide.
1; 3
What converts superoxide to H2O2?
Superoxide dismutase
Hydrogen peroxide is converted into H2O by what enzyme?
Catalase or Glutathione peroxidase (GPX)
Increase production of peroxide and/or an increased amount of reduced iron can cause peroxide to be converted into a _____
Hydroxyl radical
Nitric oxide and peroxy nitrite are produced in the ____________
Mitochondria
What enzyme produces Nitric oxide?
Nitric Oxide Synthase
In conditions where there is increased production of superoxide and/or nitric oxide, superoxide and nitric oxide can react to form _________
peroxynitrite
What is the ideal pathway for superoxide?
To be converted to H2O2 and then immediately to H2O
T or F? White blood cells produce bleach?
True
What type of cell produces superoxide, hydrogen peroxide, hydroxyl radical and hypochlorous acid?
White Blood Cells
In WBC, what is the function of ROS?
To kill bacteria and viruses
T or F? ROS can leak out of WBC and damage surrounding healthy tissue.
True
What are the environmental/external sources which can contain or stimulate ROS/RNS production in cells?
- UV light
- Ionizing radiation
- Smoking
- Air pollution
- Medications (such as acetaminophen and doxorubicin)
How do cells protect against ROS/RNS?
- Antioxidant
- Enzymatic antioxidants
- Non-enzymatic antioxidants
_____ converts a reactive species into a less reactive species.
Antioxidant
What are the 3 enzymatic antioxidants?
- Superoxide dismutase
- Catalase
- Glutathione peroxidase (GPX)
List 7 non-enzymatic antioxidants
- Glutathione (GSH)
- Coenzyme Q
- Alpha-lipoic acid
- Vitamin C
- Vitamin E
- N-acetylcystein (NAC)
- Flavonoids
______ is tripeptide consisting of cysteine, glutamate, and glycine, are synthesized in all cells of the body.
Glutathione (GSH)
What are the 2 mechanisms of how GSH can neutralize ROS/RNS/Xenobiotics?
- Hydrogen peroxide (H2O2) via GPx and 2(GSH) reacting to form glutathione disulfide (GSSG) and 2 H2O
- GSH can also be conjugated to chemicals to neutralize them.
T or F? When H2O2 is neutralized, GSH is being conjugated to it.
False, not conjugation, GSH is donating it’s H’s.
What enzyme creates a conjugation between GSH and a xenobiotic or chemical to create a Glutathione-S-Conjugate?
Glutathione-S-transferase (GST)
T or F? Conjugation can also occur without an enzyme catalyzing the reaction.
True
What happens to the Glutathione-S-Conjugate after it is formed?
It is filtered out of the body
What is used to determine the oxidative stress level in a cell?
The ratio between GSH and GSSH
High levels of GSH and low Levels of GSSG indicates that the cell is in _____ level of oxidative stress.
Low
What non-enzymatic antioxidants are produced by the body?
Glutathione, Coenzyme Q and Alpha-lipoic acid
What are the 3 details of Alpha-lipoic acid?
- Water and lipid soluble
- Can protect against free radicals in all parts of cell
- It can also enhance function of vitamin C and E
Which antioxidants are not synthesized by the body?
Vitamin C -Water Soluble
Vitamin E - Lipid Soluble (protects agains ROS/RNS damage in membranes)
N-Acetylcysteine (NAC)
Flavonoids
What does N-acetylcysteine (NAC) do?
Acts as a donor of cysteine for GSH biosynthesis
Available as a drug (mucomyst) used to treat acetaminophen overdose
The term used to describe an imbalance between ROS/RNS production and antioxidant status.
Oxidative stress
T or F? Oxidative stress causes damage to macromolecules?
True
DNA damage by ROS/RNS can lead to what?
Increase mutation and deletions in nuclear DNA and mtDNA (mitochondria DNA)
Damaged proteins by oxidation or nitration can lead to what?
Altered activity and /or function of the protein
Damage lipids by lipid peroxidation can lead to what?
Loss of membrane fluidity or altered cell signaling.
What is the ultimate outcome of damage caused by ROS/RNS?
Dysfunctional cells or cell death
What are a few diseases that are caused by oxidative stress or plays a role in the progression of the disease?
- Cancer
- Cardiovascular disease
- Alzheimer’s disease
- Parkinson’s disease
- Diabetes
- Many more
