Reactive Oxygen Species Flashcards
what is a free radical?
highly reactive radical that can initiate chain rxns.
it has a single unpaired electron
what is the non-radical tht is included in the group of reactive oxygen species?
hydrogen peroxide
what scavenges free radicals?
antioxidants!
what are the examples of free radicals?
superoxide (ROS), hydroxyl radical (ROS), nitrogen dioxide (RNOS)
what leads to free radicals?
hydrogen peroxide and peroxynitrate
why is mitochondria more susceptible to ROS damage than nuclear DNA?
has no histones
and it is close to CoQ in mitochondria
how is superoxide formed? where in the cell is it formed?
Superoxide is formed from molecular oxygen after uptake of one electron.
Superoxide is formed for example in mitochondria related to the ETC at the CoQ
level or also related to microsomal cytochromes P450.
which enzyme scavenges superoxide?
superoxide dismutase (SOD)
it takes two superoxides and smushes them togtehet! and forms hydrogen perioxide and oxygen
What results from a deficiency of this SOD enzyme? What are the clinical features (name 6)? What is another name for this disease?
A deficiency of this enzyme leads to amyotrophic lateral sclerosis (ALS) which is a degenerative disease of both upper and lower motor neurons. Superoxide dismutase deficiency can be acquired or hereditary.
The clinical features are muscle weakness, fasciculation, atrophy, dysphagia, dysarthria and hyperreflexia and it can lead to death after several years.
Another name for this disease is Lou Gehrig disease, named after the patient who was a famous baseball player.
where are superoxide dismutase found?
extracellular (copper), in cytosol(copper and zinc) and also in mitochondria (manganese)
Name the difference between hydroxyl ion and hydroxyl radical!
Hydroxyl ion OH- and hydrogen ion H+ are formed normally from water.
Hydroxyl radical OH. is formed from water by ionizing radiation.
how can hydroxyl radical be formed?
Hydroxyl radical can be formed
- by ionizing radiation
2. from hydrogen peroxide and superoxide [Haber-Weiss reaction] and
3. from hydrogen peroxide and ferrous iron [Fenton reaction].
which compound is a major radical scavenger in the blood and lungs?
Uric acid is a major radical scavenger in blood and lungs.
[on the other hand, a too high blood level can lead to crystal formation in the joints and lead to a gout attack]
what does catalase do?
takes two hydrogen peroxides and smushes them togther to form water and oxygen
where are catalases found and what do they contain?
found in peroxisomes
contain heme
10 Describe the reactions catalyzed by glutathione peroxidase when it acts on
hydrogen peroxide and when it acts on organic peroxides!
Glutathione peroxidase using hydrogen peroxide and 2 GSH, forms 2 water and
GSSG.
Glutathione peroxidase using ROOH and 2 GSH forms ROH, GSSG and water
Which trace mineral is
needed as cofactor for glutathione peroxidase?
selenium
under what conditions are ROS formation enhanced (this is bad)!
ROS formation is enhanced at high oxygen tension and by ischemic reperfusion.
what are the 3 enzymatic radical scavengers?
SOD
catalase
glutothione peroxidase
what are the non enzymatic radical scavengers
uric acid (half of the scavengers found in the blood and lungs) glutathione, bilirubin, melatonin and others.
where are dietary radical scavengers found?
in fruits and vegetables, especially in leaves and seeds. They include vitamins, PUFAs, carotenoids, flavonoids, phytochemicals, polyphenols, isoprenoidsand resveratoland some seem to be able to even scavenge hydroxyl radical
where are ROS and RNOS formed and why?
formed on purpose
in phagocyticcells of the immune system
(neutrophils, eosinophilsand monocytes/macrophages)
as human defense mechanism.
what are the important enzymes for body defense?
NADPH oxidase
myeloperoxidase
nitric oxide synthase
NADPH oxidase: what does it use, what does it form?
uses
NADPH and molecular oxygen and
forms superoxide
The enzyme is in the
plasma membrane of neutrophils and it forms superoxide in the
“respiratory burst” as defense enzyme.
myeloperoxidase: what does it use, what does it form?
uses
hydrogen peroxide and chloride ions and
forms hypochloriousacid
destroys bacteria and fungi = candida albicans
leads to the green color of pus due to the 2 heme-like groups
nitric oxide synthase: what does it use, what does it form?
uses
NADPH and arginineand
forms nitric oxide and citrulline
Describe inducible nitric oxide synthase (iNO synthase) and formation of peroxynitrite!
iNO synthase forms the radical nitric oxide (NO), which then reacts with another
radical, which is superoxide (formed by NADPH oxidase).
This reaction leads to peroxynitrite which is itself not a radical but is highly toxic.
Peroxinitrite leads also to other RNOS and to the radical nitrogen dioxide.
describe chornic granulomatous disease
Deficiency of NADPH oxidase leads to persistent bacterial infection (pneumonia)
and to granuloma in the area of infected cells. The granulomas contain sequestered
bacteria in infected cells.
The genetic defect is X-linked.
Sometimes there is also recurrent infection with aspergillus.
describe chornic granulomatous disease
Deficiency of NADPH oxidase leads to persistent bacterial infection (pneumonia)
and to granuloma in the area of infected cells. The granulomas contain sequestered
bacteria in infected cells.
The genetic defect is X-linked.
Sometimes there is also recurrent infection with aspergillus.
