Reactive Oxygen Species Flashcards
What is the Fenton reaction?
Fe2+ H2O2 = OH + Fe3 and OH-
What are 3 types of ROS?
Hydroxyl radical, superoxide, hydrogen peroxide
Why is H2O2 a ROS?
It can create a hydroxyl radical and diffuse throughout the body
What is a free radical?
an atom, molecule, or ion with unpaired valence electrons
What is the most reactive RNOS?
Peroxynitrorous acid
Reactive oxygen and free radicals initiate what?
Cell injury
What does oxygen toxicity result from?
Reactive oxygen species and free radicals
Antioxidant defenses have evolved in parallel with what?
Evolution of aerobic metabolism
How are ROS generated?
One electron transfers
What is the Harber-Weiss reaction?
O2- + h2o2 with H+ —— O2 + h2o + OH
The OH radical is especially dangerous in which cell type? Why?
RBC; leads to anemia
What is the most reactive ROS?
Hydroxyl radical
How does peroxynitrous induce damage?
Adds nitronium ions to aromatic rings, especially aromatic aa
What are 3 normal biological processes that generate superoxides?
Phase I detox (p450), ETC (CoQ), LOX and COX
What immune system cells generate ROS?
Neutrophils (respiratory burst)
Which lipids are most susceptible to oxidative damage?
PUFA
What are the 4 phases of free radical damage?
Initiation, propagation, termination, degradation
What are 3 types of damage free radicals can produce in cells?
PUFA very susceptible, amino acid residues, DNA mutation from epoxides
What are 3 ways antioxidants reduce ROS activity?
Before ROS are formed, get rid of them when they are formed, repair oxidative damage
What are the 3 antioxidant enzymes?
Glutathione peroxidase, superoxide dismutase, catalase
What is the first line of defense against oxidative damage?
Antioxidant enzymes
What is the second line of defense against ROS?
Free radical scavengers like Vit C and Vit E
What are the substrates for GPX?
Selenium
Where are GPX and selenium in the cell?
Cytosol and mitochondrial matrix
What are the substrates for SOD?
Cu, Zn (cytosol); Mn (mitochondria)
What are the substrates for CAT?
Iron and peroxisomes
GPX acts on which ROS?
H2O2
SOD acts on which ROS?
Superoxide
CAT acts on which ROS?
H2O2
Glutathione is a co substrate for which enzyme?
GPX
How do Vit C, E, and glutathione act as antioxidants?
Reducing agents
Where is vitamin E in the cell?
Membranes and lipoproteins (plasma membrane and lysosomes)
Where is Vit C in the cell?
Cytosol and mitochondria
Where does absorption if vitamin C occur?
Distal small intestine
How is vitamin C absorbed?
Sodium-dependent ascorbate transporter (SVCT)
Where is SCVT1?
Distal small intestine
How do most cells acquire vitamin C?
Through SCVT2 and GLUT transporters
What does ascorbate do as a primary antioxidant?
Neutralizes radical oxygen and nitrogen species, peroxides, and superoxides
Why must dehydroascorbate be reduced?
Has a short half life, must be reduced to avoid loss as diketogulonic acid
Regeneration of the reduced form of Vitamin C involves which reducing agents?
NADH or glutathione
Regeneration of the reduced form of Vitamin C involves which enzymes?
NADH reductase, dehydroascorbate reductase, thioredoxin reductase
What are 3 points to remember for why vitamin C is such an important dietary antioxidant?
Major water soluble antioxidant, can neutralize both oxygen and nitrogen ROS, ascorbate radical is stable
How do vitamin E and vitamin C differ as antioxidants?
Vitamin C acts as a direct antioxidant while vitamin E is a stable place to put the electrons until vitamin C can remove it
What 2 things make up vitamin E?
Tocopherols, tocotrienols
What component of vitamin E is selectively extracted in the liver?
a-tocopherol
Where does vitamin E accumulate?
Membranes and lipoproteins
How does vitamin E function as an antioxidant?
Terminates membrane lipid oxidation through single electron transfers, forming a stable tocopherol species
