Oxidative stress and antioxidant systems Flashcards
What is a free radical?
A molecule with an unpaired valence electron.
What is the oxygen paradox
Anaerobic organisms evolved first, and oxygen is inherently dangerous to them because of free radical generation, and anaerobic organisms typically don’t have antioxidant systems.
What is an oxidant
What is a reductant
Oxidant: something that oxidizes another chemical by: taking electrons, taking hydrogen, or adding oxygven
Reductant: Adds electrons, adds hydrogen, or removes oxygen.
half life of hydrogen peroxide
half life of hydroxyl radicals
H2O2, a few minutes
hydroxyl radical, nanoseconds.
What are ROS?
ROS are atoms or molecules formed by the incomplete reduction of oxygen.
Radical ROS:
Superoxide O2-
Hydroxyl radical OH-
Hydroperoxyl HO2-
Non-radical ROS:
Hydrogen peroxide H2O2
Singlet oxygen 1O2
Ozone O3
What are Reactive Nitrogen Species
Radical RNS:
Nitric Oxide NO
Nitrogen Dioxide NO2-
Non-radical:
Peroxynitrite ONOO-
What are the steps in the complete oxidation of oxygen
O2
O2- superoxide anion
H2O2 hydrogen peroxide
OH- hydroxyl radical
H2O water
What is the most biologically reactive ROS?
Hydroxyl radicals.
What are the good and bad roles of ROS?
bad: increased ROS load causes apoptosis
Damage DNA/proteins/Lipids in the cell
good: essential for microbial defense
Platelets use ROS as signaling to recruit more platelets and promote coagulation.
What enzymes remove ROS
Superoxide dysmutase
Catalse
guaiacol peroxidase (GPX)
Glutathione, not an enzyme tho
Diseases that ROS are involved in pathogenesis
Alzhemiers, Parkinsons, Schizophernia
Cancer
Cataracts
Hypertension, Atherosclerosis, Ischemia
Asthma
Chronic inflammatory disorders:
Lupus, Multiple sclerosis
Rheumatoid arthritis
Exogenous sources of radicals
Ionizing or UV radiation
Pollutants
Cigarette smoke
Drugs and xenobiotics
How does UV radiation generate free radicals?
from hydrogen peroxide.
Splits it into two hydroxyl radicals
How does gamma radiation generate ROS?
Can generate hydroxyl radicals from water.
Enzymes that generate ROS endogenously
Lipoxygenase
Xanthine oxidase
Cyclooxygenase
Cytochrom p450 Monooxygenase
NO synthase
NADPH oxidase
Byproduct of the Electron transport chain and partial oxygen reduction.
What is the common component of Cytpchrome p450 enzymes.
Heme is a cofactor
What enzyme generates ROS in the ER after alcohol consumption
CYP2E1
a mixed function oxidase (not alcohol dehydrogenase)
It is IN THE ER
Converts ethanol to acetaldehyde (Reducing it), and uses NADPH and O2 as cofactors, generating NADP+ and H2O, or can generate reactive oxygen species.
What reaction does Xanthine oxidase catalyze?
hypoxanthine, O2, and H20 -> H2O2 and xanthine
xanthine O2 and H20 –> uric acid and H2O2.
What precursor does NOS use to synthesize NO?
L-Arginine
What is the main enzyme neutrophils use to generate ROS?
NADPH oxidase.
Generates superoxide anions O2-
Adds a single electron to O2.
What is the organelle whose main function is generating ROS and RNS?
What are a few examples of eznymes in it?
Peroxisomes
NO synthase Xanthine oxidase Urate oxidase Acyl-CoA oxidase D-amino acid oxidase
What is the main enzyme neutrophils use to generate RNS? What other products can it generate?
Myeloperoxidase.
MPO uses H2O2 and NO2 (nitrite) to generate RNS intermediates
It can also generate several very strong acids:
H2O2 and Cl, Br, SCN,
hypochlorous HOCl
hypobromous HOBr
hypothiocyanous acids HOSCN
Or it can generate Tyrosyl radicals from H2O2 and Tyrosine.
List 5 endogenous anti-oxidants
Glutathione (replenished by gluathione reductase)
Catalse
Superoxide Dismutase
CoEnzyme Q-10
Cytochrome C Peroxidase
List some dietary anti-oxidants.
ACE vitamins, vitamins A, C, E
Alpha lipoic acid
N-acetyl cystine
Polyphenols
Green tea and Olive oil
Proanthocyanidins
Red wine
Blueberrys
Chocolate
Ginsengs.
