Biochemistry - Lecture 37 - Reactive Oxygen Species

Front 1

What are reactive oxygen species?

Back 1

– Is formed in many reactions for example catalyzed by superoxide dismutase and in peroxisomes by xanthine oxidase and peroxisomal b-oxidation.
– is lipid soluble and can diffuse through membranes and leads to hydroxyl radical when it is not scavenged
Accumulation of this leads in the Haber-Weiss reaction or in the Fenton reaction to hydroxyl radicals.

Front 2

What are free radicals and what are ones that leads to free radicals? And when are they formed?

Back 2

Free radicals: superoxide, hydroxyl radical, and nitrogen dioxide
Leading to free radicals: hydrogen peroxide, and peroxynitrite.
Both ROS and RNOS are formed during oxidative stress and need to be scavenged.

Front 3

What is mitochondrial DNA more susceptible to ROS damage than nuclear DNA?

Back 3

This is because mitochondria DNA does not have histones and is also close to CoQ - forms superoxide.

Front 4

What is a superoxide and where is it formed?

Back 4

It is an anion radical (O2 + e- --> O2-) and is always formed in:
-mitochondrial during ETC (CoQ)
-cytosol by microsomal cytochromes P450
- peroxisomes by cytochromes P450

Front 5

What is the function of superoxide desmutase (SOD)?

Back 5

It uses two superoxide at the same time as substrates and combines them together to make a non-radical. It makes ROS + O2.
It is found in extracellular (copper), in cytosol (copper and zinc) and also in mitochondria (manganese)

Front 6

What is hydrogen peroxide?

Back 6

– Is formed in many reactions for example catalyzed by superoxide dismutase and in peroxisomes by xanthine oxidase and peroxisomal b-oxidation.
– is lipid soluble and can diffuse through membranes and leads to hydroxyl radical when it is not scavenged
Accumulation of this leads in the Haber-Weiss reaction or in the Fenton reaction to hydroxyl radicals.

Front 7

What is a hydroxyl radical?

Back 7

It is non-enzymatically formed superoxide and hydrogen peroxide in iron-catalyzed Haber Weiss reaction. It is the most detrimental ROS and also formed during radiation (skin, mutations, cancer and death)
H2O2 + O2- lead to OH radical (Haber-Weiss)
h2O2 + Fe2(or Cu) leads to OH radical (Fenton)

Front 8

What is the function of Catalase?

Back 8

It is found in many peroxisomes and scavenges hydrogen peroxide. It contains heme and uses two hydrogen as substrates at the same time.
Hydrogen peroxide is scavenged by catalase or by glutathione peroxidase [fast reactions]
H202 + h2o2 --> 2 h2O and O2

Front 9

What is the function of glutathione peroxidase?

Back 9

Uses (selenium) as coenzyme and needs reduced glutathione and acts on hydrogen peroxide.
H2O2 plus 2 GSH (glutathione) ---> GSSG (glutathione disulfide) plus 2 H2O

Front 10

What is the difference between catalase and this?

Back 10

Difference is that they can act on organic peroxides which catalase annoy_
ROOH plus 2 GSH --->  GSSG plus ROH
They can also reverse lipid peroxidation of unsaturated fatty acids in membrane phospholipids - import for RBC.
RBC are in oxygen pressure in the lungs, molecular oxygen can act on membrane to make lipid peroxide, which if not repaired FA break and shorten and cause membrane to leak.

Front 11

What are the enzymatic radical scavengers?

Back 11

Are SOD, catalase and glutathione peroxidase
SOD - acts on superoxides
Catalase - uses two hydrogen peroxides
GSH peroxidase - acts on hydrogen peroxides, organic peroxides and lipid peroxidation reversal

Front 12

What are the non-enzymatic endogenous radical scavengers?

Back 12

Have uric avid (half of scavengers in blood and lungs). gluthatione, bilirubin, melatonin and others.

Front 13

What are dietary radical scavengers?

Back 13

These are ones found in fruits, vegetables, leaves and seeds. They include vitamins, PUFAs, carotenoids, flavonoids, phytochemicals, polyphenols, isoprenoids and resveratol and some seem to be able to even scavenge hydroxyl radical.

Front 14

What is Amyotrophic Lateral Sclerosis (ALS)?

Back 14

Is caused by the deficiency of superoxide dismutase.
Lou Gehrig's disease. The cause is unknow but 10% of ALS is due to hereditary defect of dismutase.
ALS is degenerative disease of nerve cells in brain and spinal cord. Both upper and lower motor neurons degenerate or die.
Results in difficulty breathing, head drop, and muscle weakness and onset is 40-50 years.

Front 15

What is NADPH oxidase?

Back 15

NADPH oxidase is found in neutrophil cell membranes.
The enzyme generates superoxide on purpose using molecular oxygen and NADPH. (respiratory burst).
SOD forms hydrogen peroxide.
Hydroxyl radical can be formed in the Fenton- and Haber-Weiss reactions.
Myeloperoxidase forms hypochlorous acid which destroys bacteria and fungi

Front 16

What is the function of myeloperoxidase?

Back 16

It is secreted into the phagolysosome. This enzyme uses hydrogen peroxide and chloride ions and forms hypchlorous acid (bleach) - used to fight bacteria and fungi.
It leads to green color of pus due to 2 heme-like gorups.

Front 17

What are the physiological functions and defense functions of Nitric Oxide?

Back 17

It relaxes smooth muscle, prevents platelet aggregations and functions as neurotransmitter.
Nitric oxide is formed in macrophages by inducible NO synthase - is needed for formation of RNOS as defense.
In defense, RNOS is formed which starts with nitric oxide and superoxide ----> to form peroxynitrite.
This is not a free radical but is toxic and leads other RNOS including free radical NO2.

Front 18

What is respiratory burst?

Back 18

Front 19

What is Chronic Granulomatous Disease (CGD)?

Back 19

This is due to a hereditary deficiency of NADPH oxidase. It is also know as Bridges-Good Syndrome.
It results in granulomas which contain sequestered bacteria.
Have recurrent severe infections of bacteria (pnuemonia or fungi (aspergiluus).
-Have less ROS and RNOS - X-linked

Front 20

What is Myeloperoxidase deficiency?

Back 20

Is a myeloperoxidase deficiency which leads to less production of less hypochlorous acid. Results in recurrent infections of candida albicans (fungus).
Leads to oral and genital infections.
Bacteria are destroyed by ROS and RNOS because NADPH oxidase is function by fungus needs hypochlorous acid.