Free Radical and Antioxidants Flashcards
oxygen in the ground state that has absorbed light or other sources
“excited”
- not a radical but still reactive
singlet oxygen
- generated by one-electron reduction of molecular oxygen, usually involve a metal catalyst
- not very reactive
superoxide anion
transfer of two electrons to oxygen
hydrogen peroxide
transfer of three electrons to oxygen
generates hydroxyl radical and hydroxide anion
hydroxyl radical is most reactive ROS, half-life of nanoseconds
transfer of four electrons to oxygen
water
What is a by-product of ETS?
ROS
- instead of transferring the electron to complex III, it gets put on oxygen to make superoxide anion
What organelle is a major source of ROS?
mitochondria
NADPH/cytochrome oxdiases are a source of which ROS?
superoxide anion
Xanthine oxidase is a source of which ROS?
2 peroxide is produces when reducing hypoxanthine and xanthine to uric acid
Reduction of iron and copper ions are a source of which ROS?
can donate electron to either oxygen or peroxide: superoxide anion (oxygen) and hydroxyl radical (peroxide)
How does chronic alcohol metabolism stress the liver?
1) oxidative stress from hydrogen peroxide damages membranes and kills cells
2) DNA damage from hydroxyethyl production produces mutations and predisposes to cancer
located in cytoplasm and mitochondria to convert superoxide into the less reactive oxygen intermediate hydrogen peroxide
- antioxidant
superoxide dismutase
heme-containing enzyme that detoxifies hydrogen peroxide
- antioxidant
catalase
uses the electrons from reduced glutathione to reduce hydrogen peroxide
- antioxidant
glutathione peroxidase
- water-soluble electron donor to many types of free radicals
- oxidized to dehydroascorbic acid
- antioxidant
ascorbic acid (vitamin C)
- lipid-soluble radical scavenger
- present in membranes where it prevents damage from free radicals as well as from lipid peroxidation
- antioxidant
Vitamin E (tocopherols)
- lipid-soluble compound that functions as an electron donor for the reduction of radicals such as lipid peroxides
- “quenches” the vibrating energy from the singlet oxygen
- antioxidant
Vitamin A (retinol)
- water-soluble
- metabolic antioxidant
- plant extracts: green tea, grapes, red wine, chocolate
Polyphenols (flavonoids)
major metabolic antioxidant in serum
uric acid
- lipid soluble metabolic antioxidant
- unconjugated form can donate electrons to radicals
Bilirubin
- converts back to biliverdin
What does peroxidative breakdown of polyunsaturated fatty acids (PUFAs) affect?
- integrity and function of cell membrane
- most serious damage to membranes
Summarize the process of lipid peroxidation
PUFA»Lipid Radical»Lipid Peroxide (unstable), reacts with itself»malondialdehyde (mutagenic, reacts with purine bases in DNA)
What leads to large amounts of ROS in RBCs?
high oxygen saturation
1) glutathione peroxidase
- destroys hydrogen and organic peroxides
2) superoxide dismutase
- destroys superoxide
3) catalase
- converts hydrogen peroxide
4) high concentrations of GSH, Vit C, Vit E
- directly react with ROS
5) methemoglobin reductase
how RBC control oxidative stress
Explain how methemoglobin reductase can reduce oxidative stress in RBCs
- replaces electron to the iron in heme
- repairs the oxidative damage by reducing the iron and converts methemoglobin back to Hb
Which ROS does the most damage to DNA?
hydroxyl radical
- causes DNA double strand breaks
- interferes with replication and transcription by binding to guanine bases
What does ROS cause protein damage?
- causes formation of incorrect disulfide bonds
- proteins become inactive and initiate its destruction
- free radical that acts as a powerful vasodilator
- modifies proteins in signal transduction pathways
- most effective through activation of guanylate cyclase
Nitric Oxide
- covalently modifies lipies, DNAs, and proteins
- formed from superoxide and peroxynitrate anions
- very reactive
Peroxynitrite
