oxidative phosphorylation

Question 1

describe the chemiosmotic hypothesis

Answer 1

energy input for ATP synthesis comes from proton gradient established by the movement of electrons along the electron transport chain

Question 2

how are protons moved in the electron transport chain?

Answer 2

H+ are moved from the matrix into the inner membrane space, making the inner membrane space more acidic

Question 3

what is required for the chemiosmotic hypothesis to be true?

Answer 3

inner mitochondrial membrane must be impermeable to H+

Question 4

complex I

Answer 4

NADH dehydrogenase

accepts e- from NADH, hands off to CoQ

Question 5

Complex II

Answer 5

succinate dehydrogenase

accepts e- from FADH2, hands off to CoQ

Question 6

complex III

Answer 6

cytochrome b-c1

accepts e- from CoQ, hands off to cytochrome c

Question 7

complex IV

Answer 7

cytochrome oxidase

accepts e- from cytochome C, uses E- to convert O2 –> H20

Question 8

complex V

Answer 8

ATP synthase, uses H+ gradient to form ATP

Question 9

most of the complexes are a mix of mito and nuclear DNA, what is the exception?

Answer 9

complex II is only nuclear DNA (also smallest with only 4 subunits)

Question 10

diseases assoc with complex I and complex IV

Answer 10

both assoc with genetic disease and also seen in neurologic diseases

Question 11

disease assoc with complex II

Answer 11

genetic d/o and paraganglioma

Question 12

disease assoc with complex V

Answer 12

cancer

Question 13

which complexes have iron-sulfur centers?

Answer 13

I, II, III

Question 14

structure of iron-sulfur centers

Answer 14

iron atoms complexed with sulfur from cysteine, responsible for maintaining correct protein structure

Question 15

what is one reason for fatigue in iron deficiency?

Answer 15

if iron is deficient, then iron-sulfur centers will be decreased, leading to improper configuration of iron-sulfur centers = effects on complexes I, II, III = decreased ATP production

Question 16

MOA of doxorubicin

Answer 16

inhibits Coenzyme Q thereby inhibiting flow of electrons in the ETC and inhibiting ATP production

Question 17

2 undesired effects of doxirubicin

Answer 17

cardiotoxic (binds cardiolipin)

forms free radicals that may damage mito membrane

Question 18

describe Reye’s syndrome

Answer 18

occurs with aspirin use during viral infection, causes mitochondria to rupture leading to decreased ATP synthesis and also decreased ability to form urea = NH4+ levels accumulate and hepatic coma results, more pronounced effect in children

Question 19

what controls flux through the ETC?

Answer 19

energy charge of the cell (ATP/ADP), increased ADP will increase flux through ETC

Question 20

describe using respirometer to measure mitochondrial efficiency

Answer 20

use respirometer to measure O2, should see that O2 consumption increases when ADP added if mito are working properly

Question 21

how many H+ will be pumped per NADH

Answer 21

10
4 @ I
4 @ III
2 @ IV
= 2.5 ATP/NADH

Question 22

how many H+ will be pumped per FADH2

Answer 22

6
4 @ III
2 @ IV
= 1.5 ATP/FADH2

Question 23

what are “chemical uncouplers”?

Answer 23

substances that disrupt the H+ gradient in the mitochondria by allowing H+ to pass into matrix by other means and NOT by ATP synthase

Question 24

4 examples of chemical uncouplers

Answer 24

2,4-dinitrophenol
FCCP
CCCP
aspirin/salicylate

Question 25

describe effects of uncoupling by salicylate

Answer 25

“partial” uncoupler at high concentrations
due to uncoupling, ATP will decrease and AMP will increase = increased glycolysis by stimulation of phosphofructokinase = increased lactate and lactic acidosis

Question 26

what is the “uncoupler” found in brown fat?

Answer 26

thermogenin

Question 27

what is the function of brown fat?

Answer 27

heat generation/thermoregulation in infants- when norepinephrine stimulates fat lipolysis, thermogenin allows brown fat cells to generate heat

Question 28

uncoupling effects of thyroid hormone

Answer 28

thyroid hormone is a partial uncoupler = pts with hyperthyroidism will feel hot, also will not be able to derive max energy via oxphos

Question 29

what is “ANT”?

Answer 29

ATP-ADP antiporter in the mito inner membrane, exports newly synthesized ATP and imports ADP

Question 30

what is the importance of creatine phosphate?

Answer 30

synthesized by creatine kinase, it is a stored form of energy present in the inner membrane space in muscle mitochondria, the phosphate can be quickly transferred to ADP to make ATP

Question 31

how is the mitochondrial permeability transition pore formed?

Answer 31

ANT associates with VDAC

Question 32

what are the consequences of MPTP formation?

Answer 32

allows mito membrane to be more permeable, can result in cell swelling and apoptosis

Question 33

why are “shuttles” needed?

Answer 33

to move the NADH that was synthesized during glycolysis into the mitochondria so that it can be used in the ETC

Question 34

where is the glycerol-phosphate shuttle? MOA?

Answer 34

found in skeletal mm and brain
NADH in cytosol gives e- to FADH2
= 1.5 ATP per NADH

Question 35

where is the malate-aspartate shuttle? MOA?

Answer 35

found in liver, kidney, heart
NADH in cytosol gives e- to oxaloacetate forming malate
malate travels into mitochondria and gives e- to NAD+ to yield NADH and reform oxaloacetate
=2.5 ATP per NADH

Question 36

why is the rho zero cell system used?

Answer 36

in a person with mito disease, use this to determine if the problem is coming from nuclear DNA or mito DNA contributions

Question 37

how does rho zero system work?

Answer 37

-pts cell is enucleated, only mito remain
- rho zero cell has mito killed off
cells are joined to make cybrid
if mito function in cybrid is abnormal, then pts mito are abnormal

Question 38

what is the effect of statins on ETC?

Answer 38

statins will decrease Coenzyme Q-10