41-53 Flashcards
Free radicals
free radical
species that contains 1 or more unpaired electrons
EG of radicals
O2-. superoxide anion radical O2.-2 peroxide radical .OH Hydroxyl radical No. Nitric oxide radical RO2. Peroxyl radical 1O2 singlet oxygen H. Hydrogen radical
when 2 FR meet
unpaired electrons join to form pair and both radicals are lost
oxidative stress
when FR generations exceeds capacity of AO defenses
diseases associated with superoxide anion radicals
O2-.
inflammatory disease=glomerulonephritis= inflammation of glomeruli of kidneys
radiation induced cancer
strokes
wilson’s disease= Accumulation of Cu
source of FR generation in body
Endothelial cell lining blood vessel respond to certain stimuli (EG ACH (Para-Sym NS) or bradykinin) by secreting Nitric Oxide radical = relaxes smooth muscle = vasodilation = decreases blood pressure
When water exposed to IR = H20–> H. radical + .OH
Hydroxyl radical more dangerous than nitric oxide radical as it is extremely reactive
why is hydroxyl radical so dangerous
extremely reactive, attacks to all molecules in cells, it fragments DNA(carcinogensis)/proteins/carbohydrates
initiates lipid peroxidation
will start a FR chain reaction to degrade tissue
SOR formed by
O2-. adding 1 electron to Oxygen
is SOR more or less reactive to hydroxyl radical
O2-. < .OH
what happens when SOR reacts to NO.
opposes vasodilator action of nitric oxide radical = acts as vasoconstrictor
is SOR good or bad
O2-. can be useful
acts as growth regulators due to continuous generation in small amounts by lymphocytes and fibroblasts
useful in phagocytosis when NADPH-Dependent superoxide synthase/enzyme activate to produce large quantities of 02-. to kill invading pathogens
how is singlet oxygen 1O2 formed
when photosensitizing agents react w/ ground state oxygen O2
1^S + hf ->3^S*
3^S*+3^O2->1^S + 1^O2
1^S = ground singlet state
hf = photosensitizing agent
3^S*=oxidised photosensitiser FR
1^O2=singlet Oxygen
EG photosensitizing agent=porphyrin
Accumulation of porphyrin will damage skin to form singlet oxygen
==this can be useful since hematoporphyrin is taken up by cells, so by using fluorescents we can identify sites of tumor
Peroxyl radicals will collide w/ each other to form small amounts of singlet O2
how is hydrogen peroxide formed and is this dangerous
oxidation of certain AA in peroxisomes, yes since when H2O2 reacts w/ superoxide anion radical = hydroxyl radical
why are cell membranes prone to FR attack
free poly unsat FA on cell membranes are readily attacked and oxidize into lipid peroxides = damages body cells and releases toxic products
initiation and propagation of lipids
I=RH+X.->R.+XH RH=unsat lipid X.=Radical R.=Lipid radical XH=EG. Water
P= R.+O2->ROO. ROO.+RH->ROOH+R. ROO.= peroxyl radical ROOH=lipid peroxide R.=lipid radical
what can Peroxyl radicals do
abstract H atoms from adjacent PUFA side chains to propagate FR chain reaction of lipid peroxidation
reacts w/ AA residues on proteins = impairs function
oxidizes cholesterol = products will promote atherosclerosis
2 RO2. react with each other:
2RO2. ->R2O4->R2O2 + 1O2 singlet oxygen
decomposition and termination of lipid peroxidation
D:
H2O2/ROOH+Fe2+-complex->Fe3+-complex+-OH+.OH/.OR
ROOH+Fe3+-complex->Fe2+-complex + H+ + ROO-
HOOH=hydrogen peroxde ROOH=lipid hydroperoxide Fe2+-complex=ferrous ion complex Fe3+ complex= ferric ion complex -OH=hydroxide ion .OH=hydroxyl radical ROO-=Peroxyl ion .RO=alkoxy radical
T=R.R.->RR
R.+RO2.->R2O2
ROO.+ROO.->R2O4
R.=C centered radical
RO2.=Lipid peroxyl radical
consequences of lipid peroxidation
increased membrane rigidity, decreased activity of membrane bound enzymes EG Na+ pumps, altered activity of membrane receptors and altered permeability and function of membrane
enzymatic AO EGs
Superoxide dismutase SOD, Catalase and Glutathione Peroxidase
Fe bound to transferrin and Cu bound to ceruloplasmin to prevent lipid peroxidation
Superoxide dismutase function
Superoxide dismutase in mitochondria and cytosol.
catalyses removal of superoxide anion by 10000 fold
2O2-. + SOD -> O2+H2O2
in peroxisomes, AA oxidases involved
catalase function
found in peroxisomes in E
degrades H2O2-> water and oxygen 3O2/triplet oxygen
it finishes the detoxification reaction started by Superoxide dismutase
Glutathione peroxidase reaction and function
Glutathione peroxidase = G-Px - group of enzymes that degrade hydrogen peroxide and PUFA peroxides to metabolize released peroxides
Non-enzymatic AOs EGs
Alpha-Tocopherol/ Vitamin E and Vit C
Alpha-Tocopherol/Vit E function
Alpha-tocopherol/Vit E is a lipid-soluble AO and reacts to peroxyl radicals faster than peroxyl radicals and PUFAs.
It reacts w/ the RO2./Peroxyl radicals to migrate to membrane surface to be reduced back to alpha tocopherol in reaction w/ Vit C/ascorbic acid to minimize rate of Lipid peroxidation
Ascorbic Acid/Vit C function
helps in function of alpha-tocopherol/vit E to minimize rate of lipid peroxidation
what does oxidative stress lead to
atherosclerosis = narrowing of arterial lumen = myocardial and cerebral infarcts(tissue death due to inadequate blood supply) = tissue ischemia
also oxidative stress leads to CNS injury=stroke
how is atherosclerosis caused
due to the impaired endothelium, monocytes adhere here and develop into macrophages to produce superoxides
also lipid-laden foam cells found in the early lesions will undergo peroxidation here
which places in the human body are more prone to oxidative stress and why
brain and spinal cord
their membranes are rich in PUFA side chains but the AO activity is low. So any injury can release intracellular ions that accelerate FR reactions and peroxidation of brain lipids.
Also NS is rich in epinephrine, norepinephrine, dopamine, these hormones can react with oxygen and form superoxide radicals that participate in FR reactions
what is used to reduce damage caused by oxidative stress in brain and spinal cord
chelating agents can bind to Iron to inhibit peroxidation of brain homogenates and prevent it accelerating FR reactions. But these complexes must cross the brain-blood barrier.
what makes AO efficient
must protect proteins/DNA from oxidative damage
their method of protection must be to scavenge radicals, prevent radical formation, repair the damage done by radicals
