reactive oxygen species Flashcards
define “oxidative stress”
when rate of ROS/RNOS production exceeds their removal by cellular defenses
most potent ROS
hydroxyl radical (OH.)
how is OH. produced? (3)
fenton rxn
haber-weiss rxn
single electron reductions of O2
describe the fenton reaction
H2O2 treated with Fe2+ –> OH. + OH-
describe the Haber-Weiss reaction
O2- + H2O2 –> O2 + H2O + OH.
what is lipofuscin?
characteristic of aging cells that is a result of ROS action on cell membranes (like membrane per oxidation)
what is the “kinetic barrier” mechanism?
describes the process by which ROS intermediates are tightly bound in the active site and are unable to escape and damage the cell
what is the exception to “kinetic barrier”?
H2O2 = it is normally released
what is the general structure of a monooxygenase? (3)
- electron donor substrate (like NADPH)
- coenzyme (like FAD)
- metal ion (like Fe)
what is a common example of monooxygenase?
cytochrome p450 superfamily
what is the MOA of cytochrome p450 enzymes?
will hydroxylate (add OH) compounds so they can be excreted, occurs mainly in the liver
describe NO at low concentrations
NO at low concentrations is a neurotransmitter and hormone that causes vasodilation
describe NO at high concentrations
NO at high concentrations will react with O2 or O2- to form RNOS
what diseases are assoc with high levels of RNOS?
neurodegenerative disease (parkinsons) and chronic inflammatory disease (RA)
what is the only “safe” nitrogen species in the body?
nitrate - all other forms are RNOS
what can occur at coenzyme Q regarding ROS?
for a very small amount of e- passing through ETC, O2 will be prematurely reduced by CoQH. to yield O2- radical, occurs more at complexes I and II
effect of ionizing radiation on ROS
ionizing radiation can cause the splitting of water to form OH.
what is 8-hydroxyguanine?
- forms secondary to the interaction between guanine and OH.
- can be measured to estimate oxidative damage within a cell
useful ROS in thyroid
hydrogen peroxide needed to attach iodine to thyroglobulin in synthesis of thyroxine
useful ROS in macrophages and neutrophils
generate ROS to kill phagocytosed microbes
useful ROS in neutrophils only
use myeloperoxidase to catalyze reaction of H2O2 and Cl- to yield hypochlorite ion = strong antiseptic
chronic granulomatous disease
defect in subunit of NADPH oxidase = impaired ability to form O2- = impaired ability to kill phagocytksed microbes
function of catalase
breaks down H2O2 into H2O and O2
3 enzymes that help cells deal with ROS
1-superoxide dismutase
2- catalase
3- glutathione peroxidase and reductase
MOA of superoxide dismutase
converts O2- to H2O2
2 forms of superoxide dismutase
SOD-1 = in cytosol, uses Cu-Zn SOD-2 = in mitochrondria, uses Mn
3 aa that compose the reduced form of gluthatione (GSH)
glycine
cysteine
glutamate
MOA of glutathione peroxidase
uses GSH to convert H2O2 to H2O
MOA of glutathione reductase
uses NADPH to convert GSSG back to GSH so that GSH can continue to deal with free radicals
source of NADPH for glutathione reductase
pentose phosphate pathway
what vitamin protects against membrane per oxidation?
vitamin E
