Reactive Oxygen Species

Question 1

what is a free radical?

Answer 1

highly reactive radical that can initiate chain rxns.

it has a single unpaired electron

Question 2

what is the non-radical tht is included in the group of reactive oxygen species?

Answer 2

hydrogen peroxide

Question 3

what scavenges free radicals?

Answer 3

antioxidants!

Question 4

what are the examples of free radicals?

Answer 4

superoxide (ROS), hydroxyl radical (ROS), nitrogen dioxide (RNOS)

Question 5

what leads to free radicals?

Answer 5

hydrogen peroxide and peroxynitrate

Question 6

why is mitochondria more susceptible to ROS damage than nuclear DNA?

Answer 6

has no histones

and it is close to CoQ in mitochondria

Question 6

how is superoxide formed? where in the cell is it formed?

Answer 6

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.

Question 7

which enzyme scavenges superoxide?

Answer 7

superoxide dismutase (SOD)

it takes two superoxides and smushes them togtehet! and forms hydrogen perioxide and oxygen

Question 8

What results from a deficiency of this SOD enzyme? What are the clinical features (name 6)? What is another name for this disease?

Answer 8

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.

Question 9

where are superoxide dismutase found?

Answer 9

extracellular (copper), in cytosol(copper and zinc) and also in mitochondria (manganese)

Question 10

Name the difference between hydroxyl ion and hydroxyl radical!

Answer 10

Hydroxyl ion OH- and hydrogen ion H+ are formed normally from water.
Hydroxyl radical OH. is formed from water by ionizing radiation.

Question 11

how can hydroxyl radical be formed?

Answer 11

Hydroxyl radical can be formed

1. by ionizing radiation
   2. from hydrogen peroxide and superoxide [Haber-Weiss reaction] and
   3. from hydrogen peroxide and ferrous iron [Fenton reaction].

Question 12

which compound is a major radical scavenger in the blood and lungs?

Answer 12

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]

Question 13

what does catalase do?

Answer 13

takes two hydrogen peroxides and smushes them togther to form water and oxygen

Question 14

where are catalases found and what do they contain?

Answer 14

found in peroxisomes

contain heme

Question 15

10 Describe the reactions catalyzed by glutathione peroxidase when it acts on
hydrogen peroxide and when it acts on organic peroxides!

Answer 15

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

Question 16

Which trace mineral is

needed as cofactor for glutathione peroxidase?

Answer 16

selenium

Question 17

under what conditions are ROS formation enhanced (this is bad)!

Answer 17

ROS formation is enhanced at high oxygen tension and by ischemic reperfusion.

Question 18

what are the 3 enzymatic radical scavengers?

Answer 18

SOD
catalase
glutothione peroxidase

Question 19

what are the non enzymatic radical scavengers

Answer 19

uric acid (half of the scavengers found in the blood and lungs) glutathione, bilirubin, melatonin and others.

Question 20

where are dietary radical scavengers found?

Answer 20

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

Question 21

where are ROS and RNOS formed and why?

Answer 21

formed on purpose
in phagocyticcells of the immune system
(neutrophils, eosinophilsand monocytes/macrophages)
as human defense mechanism.

Question 22

what are the important enzymes for body defense?

Answer 22

NADPH oxidase
myeloperoxidase
nitric oxide synthase

Question 23

NADPH oxidase: what does it use, what does it form?

Answer 23

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.

Question 24

myeloperoxidase: what does it use, what does it form?

Answer 24

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

Question 25

nitric oxide synthase: what does it use, what does it form?

Answer 25

uses
NADPH and arginineand
forms nitric oxide and citrulline

Question 26

Describe inducible nitric oxide synthase (iNO synthase) and formation of peroxynitrite!

Answer 26

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.

Question 27

describe chornic granulomatous disease

Answer 27

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.

Question 28

describe chornic granulomatous disease

Answer 28

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.