reactive oxygen species

Question 1

define “oxidative stress”

Answer 1

when rate of ROS/RNOS production exceeds their removal by cellular defenses

Question 2

most potent ROS

Answer 2

hydroxyl radical (OH.)

Question 3

how is OH. produced? (3)

Answer 3

fenton rxn
haber-weiss rxn
single electron reductions of O2

Question 4

describe the fenton reaction

Answer 4

H2O2 treated with Fe2+ –> OH. + OH-

Question 5

describe the Haber-Weiss reaction

Answer 5

O2- + H2O2 –> O2 + H2O + OH.

Question 6

what is lipofuscin?

Answer 6

characteristic of aging cells that is a result of ROS action on cell membranes (like membrane per oxidation)

Question 7

what is the “kinetic barrier” mechanism?

Answer 7

describes the process by which ROS intermediates are tightly bound in the active site and are unable to escape and damage the cell

Question 8

what is the exception to “kinetic barrier”?

Answer 8

H2O2 = it is normally released

Question 9

what is the general structure of a monooxygenase? (3)

Answer 9

• electron donor substrate (like NADPH)
• coenzyme (like FAD)
• metal ion (like Fe)

Question 10

what is a common example of monooxygenase?

Answer 10

cytochrome p450 superfamily

Question 11

what is the MOA of cytochrome p450 enzymes?

Answer 11

will hydroxylate (add OH) compounds so they can be excreted, occurs mainly in the liver

Question 12

describe NO at low concentrations

Answer 12

NO at low concentrations is a neurotransmitter and hormone that causes vasodilation

Question 13

describe NO at high concentrations

Answer 13

NO at high concentrations will react with O2 or O2- to form RNOS

Question 14

what diseases are assoc with high levels of RNOS?

Answer 14

neurodegenerative disease (parkinsons) and chronic inflammatory disease (RA)

Question 15

what is the only “safe” nitrogen species in the body?

Answer 15

nitrate - all other forms are RNOS

Question 16

what can occur at coenzyme Q regarding ROS?

Answer 16

for a very small amount of e- passing through ETC, O2 will be prematurely reduced by CoQH. to yield O2- radical, occurs more at complexes I and II

Question 17

effect of ionizing radiation on ROS

Answer 17

ionizing radiation can cause the splitting of water to form OH.

Question 18

what is 8-hydroxyguanine?

Answer 18

• forms secondary to the interaction between guanine and OH.
• can be measured to estimate oxidative damage within a cell

Question 19

useful ROS in thyroid

Answer 19

hydrogen peroxide needed to attach iodine to thyroglobulin in synthesis of thyroxine

Question 20

useful ROS in macrophages and neutrophils

Answer 20

generate ROS to kill phagocytosed microbes

Question 21

useful ROS in neutrophils only

Answer 21

use myeloperoxidase to catalyze reaction of H2O2 and Cl- to yield hypochlorite ion = strong antiseptic

Question 22

chronic granulomatous disease

Answer 22

defect in subunit of NADPH oxidase = impaired ability to form O2- = impaired ability to kill phagocytksed microbes

Question 23

function of catalase

Answer 23

breaks down H2O2 into H2O and O2

Question 24

3 enzymes that help cells deal with ROS

Answer 24

1-superoxide dismutase
2- catalase
3- glutathione peroxidase and reductase

Question 25

MOA of superoxide dismutase

Answer 25

converts O2- to H2O2

Question 26

2 forms of superoxide dismutase

Answer 26

SOD-1 = in cytosol, uses Cu-Zn
SOD-2 = in mitochrondria, uses Mn

Question 27

3 aa that compose the reduced form of gluthatione (GSH)

Answer 27

glycine
cysteine
glutamate

Question 28

MOA of glutathione peroxidase

Answer 28

uses GSH to convert H2O2 to H2O

Question 29

MOA of glutathione reductase

Answer 29

uses NADPH to convert GSSG back to GSH so that GSH can continue to deal with free radicals

Question 30

source of NADPH for glutathione reductase

Answer 30

pentose phosphate pathway

Question 31

what vitamin protects against membrane per oxidation?

Answer 31

vitamin E