Reactive Oxygen Species

Question 1

Free Radical

Answer 1

Molecule that has a single unpaired electron in an orbital and is highly reactive. Are scavenged by antioxidants.

Question 2

What are examples of free radicals?

Answer 2

Superoxide, hydroxyl radical, nitric oxide, nitrogen dioxide

Question 3

What molecules can lead to free radicals?

Answer 3

Hydrogen peroxide and peroxynitrite

Question 4

What can enhance ROS formation?

Answer 4

High oxygen tension (supplemental oxygen for COPD), hypoxia, carbon monoxide poisoning, ischemic reperfusion, high levels of acetaldehyde from alcohol abuse

Question 5

How is superoxide formed in the Electron transport chain?

Answer 5

The one electron reduced from CoQH is free in the membrane and can accidentally transfer an electron to dissolved oxygen, forming superoxide

Question 6

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

Answer 6

It does not have histones, and is close to CoQ

Question 7

When is superoxide (anion radical) formed?

Answer 7

In the mitochondria during the ETC (coQ), in the cytosol by microsomal cytochromes P450, and in peroxisomes by cytochromes P450

Question 8

Superoxide Dismutase (SOD)

Answer 8

Used two superoxides at the same time as substrates (very efficient and fast).

Question 9

Where can you find superoxide dismustase?

Answer 9

Extracellular (copper), cytosol (copper and zinc),and mitochondria (manganese) and

Question 10

Hydrogen Peroxide is formed…

Answer 10

In SOD catalyzed reactions, xanthine oxidase catalyzed reactions, B-oxidation of very long chain fatty acids in peroxisomes.

Question 11

When hydrogen peroxide is not salvaged it…

Answer 11

Diffuses through membranes and leads to hydroxyl radicals in Haber-Weiss and Fenton reactions

Question 12

How is hydroxyl radical (OH-) formed?

Answer 12

Non-ezymatically formed from hydrogen peroxide when it acts with superoxide or ferrous ions

Question 13

What can scavenge hydrogen peroxide?

Answer 13

Catalase or glutathione peroxidase

Question 14

Catalase

Answer 14

Found mainly in peroxisomes and used hydrogen peroxide for detoxification of toxins. Contains heme and binds two hydrogen peroxides and substrates at the same time

Question 15

Glutathione Peroxidase

Answer 15

Can scavenge hydrogen peroxide. Needs two reduced glutathione molecules (2 GSH) to act on hydrogen peroxide. Uses selenium as a cofactor.

Question 16

What does a crushing injury lead to?

Answer 16

Hydroxyl radicals due to the loss of sequestration of iron

Question 17

What are some nonenzymatic endogenous radical scavengers?

Answer 17

Uric acid (can lead to gout) is half of the scavengers found in blood and lungs. Glutathione. Bilirubin (could lead to jaundice)

Question 18

What are some examples of dietary radical scavengers?

Answer 18

Vitamins, PUFAs, carotenoids, flavonoids, phytochemicals, polyphenols, isoprenoids, and reservatol.

Question 19

Amyotrophic Lateral Sclerosis (ALS)

Answer 19

Lou Gherigs. Caused by a deficiency of superoxide dismustase (SOD). Mostly idiopathic, but can be a genetic defect. Degenerative disease of the upper ad lower motor neurons that control voluntary muscle movement. Leads to difficulty breathing (vocal cord dysfunction), head drop, muscle weakness. Onset after 40-50 years of age

Question 20

NADPH oxidase

Answer 20

Used NADPH and molecular oxygen to form superoxide. Used in phagocytic cells. Found in the cell membrane of neutrophils. Generates superoxide for respiratory burst.

Question 21

Myeloperoxidase

Answer 21

Uses hydrogen peroxide and chloride ions to form hypochlorous acid (bleach). Used in phagocytic cells, secreted into the phagolysosome. Leads to the coloration of pus, due to two heme link groups

Question 22

Inducible nitric oxide synthase

Answer 22

Used NADPH and arginine to from nitric oxide and citrulline

Question 23

Physiological Functions of Nitric Oxide

Answer 23

Relaxes smooth muscle, prevents platelet aggregations, functions as a neurotransmitter in the brain. Formed in macrophages by inducible NO synthase.

Question 24

Chronic Granulomatous Disease (CGD)

Answer 24

Granulomas contain sequestered bacteria in infected cells. Recurrent severe infections by bacteria (pneumonia) or fungi (aspergillus). Mostly X-linked. Hereditary NADPH oxidase deficiency.

Question 25

Myeloperoxidase Deficiency

Answer 25

Recurrent severe infections by Candida albicans caused by decreased formation of HOCL (bleach). Bacteria are still destroyed by hydroxyl radicals and peroxynitrate as superoxide and nitric oxide can be formed. Results in oral and genital infections, and sometimes, systemic infections.