Lecture 9 - Oxygen toxicity and free radicals

Question 1

What ions can catalyze the formation of a free radical?

Answer 1

Fe2+, Cu+

Question 2

What is the Haber-Weiss reaction?

Answer 2

H2O2 + Superoxide (O2-) + H(+) => O2 + H2O + *OH (radical)

Question 3

What is the Fenton reaction?

Answer 3

H2O2 + Fe2+ => OH- + *OH (Free radical) + Fe3+

Question 4

Explain the significance of CoQ. Where is it found?

Answer 4

It contributes significantly to ROS by reacting with O2, between lipid layers of the inner mitochondrial membrane.

Question 5

What are the major centers of mitochondrial ROS creation?

Answer 5

CoQ, complex I, and cytochrome b of complex III

Question 6

Oxidase

Answer 6

Transfer electron from substrate to O2 forming H2O or H2O2.

Question 7

Oxygenases

Answer 7

Incorporate one or both O2 atoms into the substrate

Question 8

Explain the significance of of xanthine oxidase. For what pathology does it play a significant role in etiology?

Answer 8

It is an important enzyme in PURINE degradation. Oxidizes hypoxanthine to xanthine, and xanthine to uric acid generating H2O2.

Question 9

Explain the unusual progression that occurs when xanthine oxidase forms oxygen radicals.

Answer 9

Xanthine dehydrogenase (encounters Ca2+ and proteases) => xanthine oxidase (which can react with O2 to form *O2-, H2O2, and *OH

Question 10

Explain the role of allopurinol in treating gout.

Answer 10

Allopurinol is a purine analog and is a structural isomer of hypoxanthine. It’s active metabolite, oxypurinol, prevents the conversion of hypoxanthine to xanthine and thus reducing uric acid build-up, which can crystalize and produce pain

Question 11

What type of enzyme is cytochrome P450? Where is it located?

Answer 11

Oxygenase, smooth ER of hepatic cells

Question 12

Where do the e- for P450 come from?

Answer 12

NADPH

Question 13

What synthetic function do cytochrome P450s possess?

Answer 13

Synthesize steroid hormones

Question 14

What are the two components of a cytochrome P450? What is the function of each?

Answer 14

1) Reductase (oxidizes NADP+)

2) P450 - add oxygens to substrate

Question 15

What are the reactant and enzymes that lead to the formation of nitric oxide?

Answer 15

Reactants: Arginine, O2 (& NADPH for electrons)

Question 16

O2-

Answer 16

Superoxide anion - produce by electron transport, cannot diffuse far before reacting

Question 17

RCOO*

Answer 17

Organic peroxide radical - happens during fat degradation

Question 18

R*

Answer 18

Organic free radical produced from RH by OH* attack

Question 19

HOCl

Answer 19

Produced by neutrophils during respiratory burst. Toxic through halogenation.

Question 20

NO*

Answer 20

Nitric oxide - diffuses freely but rapidly complexes with metals

Question 21

HO*

Answer 21

Hydroxyl radical - Most biologically potent radical. Produced from H2O2 by the Fenton reaction in the presence of Fe2+ or Cu+

Question 22

What are the major ROS production sites in mitochondria?

Answer 22

CoQ, FeS centers of complex I, cytochrome oxidase

Question 23

How would you measure lipid damage by ROS?

Answer 23

Measure serum/urine malondialdehyde

Question 24

What vitamin is capable of terminating a free radical chain reaction?

Answer 24

E

Question 25

What can be used to measure the amount of oxidative damage in cells?

Answer 25

8-hydroxy-guanidine

Question 26

What is the significance of adjacent guanine bases?

Answer 26

Mutational hotspots

Question 27

Glutathione peroxidase

Answer 27

Converts peroxide to water, and lipid peroxides to alcohols. Some require selenium.