Block 2 OXPHOS

Question 1

What is anaerobic respiration?

Answer 1

The first phase of OXPHOS, in which ox of fuels transfers e- to NAD+ and FAD

Question 2

What is oxidative phosphorylation?

Answer 2

Energy from NADH and FADH2 and red of O2 to H2O –> high energy P bonds of ATP

Question 3

What is chemiosmotic hypothesis?

Answer 3

Proton gradient across IMM established by ETC provides energy for ATP synthesis

Question 4

What are the pHs of the mitochondrial cytosol and matrix? What accounts for this difference?

Answer 4

Cyt: 6.88; Mat: 7.78

Due to the proton gradient established by the ETC

Question 5

What is complex 1 of the ETC, and what does it do?

Answer 5

NADH DH, converts NADH + H+ to NAD+, pumps out 4 H+, and transfers e- to CoQ

Question 6

What is complex 2 of the ETC, and what does it do?

Answer 6

Succinate DH, converts succinate to fumarate, transfers e- to CoQ

Question 7

What is complex 3 of the ETC, and what does it do?

Answer 7

Cytochrome b-c1, pumps out 4 H+, accepts e- from CoQ and transfers e- to cytochrome C

Question 8

What is complex 4 of the ETC, and what does it do?

Answer 8

Cytochrome oxidase, converts 2H+ + ½ O2 to H2O, accepts e- from cytC, pumps out 2 H+

Question 9

What is complex 5 of the ETC, and what does it do?

Answer 9

ATP synthase, uses 4H+ flowing into the matrix to convert ADP + Pi to ATP

Question 10

Altered functioning of which ETC complex may contribute to PD, SZ, and diabetes?

Answer 10

Complex 1, NADH DH

Question 11

Altered functioning of which ETC complex is commonly seen in paraganglioma cancer? What is special about this complex?

Answer 11

Complex 2, succinate DH

This is the only ETC complex encoded only by nuclear DNA

Question 12

Altered functioning of which ETC complex may contribute to AD and maybe hypoxic cancer cells?

Answer 12

Complex 4, cytochrome oxidase

Question 13

Which ETC complex may be found on the surface of some cancer cells?

Answer 13

Complex 5, ATP synthase

Question 14

Which ETC complex uses prosthetic groups Fe-S and heme b & c, and is inactivated by antimycin, demerol, and Fe deficiency?

Answer 14

Complex 3, cytochrome b-c1 complex

Question 15

Which ETC complex uses prosthetic groups FAD and Fe-S and is inactivated by malonate?

Answer 15

Complex 2, succinate DH

Question 16

Which ETC complex uses prosthetic group heme c and is inactivated by Fe deficiency?

Answer 16

Cytochrome C

Question 17

Which ETC complex uses prosthetic groups FMN and Fe-S and is inactivated by rotenone and riboflavin deficiency?

Answer 17

Complex 1, NADH DH

Question 18

Which ETC complex uses prosthetic groups heme a and Cu, and is inactivated by cyanide, CO, ischemia, Fe/Cu deficiency?

Answer 18

Complex 4, cytochrome oxidase

Question 19

Which ETC complex uses prosthetic group CoQ and is inactivated by generation of free radicals and doxorubicin?

Answer 19

Coenzyme Q/ubiquinone

Question 20

What is an Fe-S center?

Answer 20

Prosthetic groups with 2,3,4,8 Fe atoms and cysteine sulfur atoms, which hold groups in place within protein and provide sulfur ligands

Question 21

Why might patients with iron deficiency anemia experience fatigue?

Answer 21

The Fe-S centers and Fe-containing cytochromes in ETC are also Fe-deficient, leading to lack of e- transport for ATP production

Question 22

How does doxorubicin work?

Answer 22

Binds cardiolipin, inhibits succ ox, inhibits ATP synthase, forms free radicals

Question 23

What is Reye’s syndrome?

Answer 23

Following URI, chicken pox, use of aspirin impairs energy metabolism, resulting in inability to incorporate ammonia into urea –> hepatic coma

Question 24

How much energy liberated during complete oxidation of glucose is recaptured by glycolysis and OXPHOS?

Answer 24

30%

Question 25

What are chemical uncouplers? What is an example?

Answer 25

Proton ionophores that carry H+ across membranes, allowing PMF to collapse; salicylate (degradation product of aspirin)

Question 26

What is thermogenin?

Answer 26

A natural uncoupler that promotes generation of heat, stimulated by norepi

Question 27

How does thyroid hormone affect OXPHOS?

Answer 27

Unclear; effectively uncouples OXPHOS, and decreases efficiency of energy derivation from fuel, results in increase in heat production

Question 28

What is creatine kinase?

Answer 28

Forms creatine phosphate, which stores P for quick transfer to ADP when ATP needed for muscle contraction

Question 29

What are the components of the mitochondrial permeability transition pore (mPTP)?

Answer 29

ANT (IMM) regulated by cyclophilin D binds VDAC (OMM), which binds Bcl2 and Bax

Question 30

How does the glycerol-phosphate shuttle work?

Answer 30

DHAP + NADH –> glycerol-3-P + NAD+ by cytosolic G3P DH. Mito G3P DH makes FADH2, transfers to QH2 and regenerates DHAP

Question 31

How does the malate-aspartate shuttle work?

Answer 31

Malate carries H from NADH into matrix, converts to OAA with loss of H, OAA –> a-kg by glutamate –> aspartate (and reverse in cytoplasm)

Question 32

Where are the glycerol-phosphate and malate-aspartate shuttles located?

Answer 32

G-P: skeletal muscle, brain

M-A: liver, kidney, heart

Question 33

How many ATP molecules can be synthesized from a pair of electrons using each of the shuttles?

Answer 33

G-P shuttle: 1.5 ATP because of e- transfer to FADH2

M-A shuttle: 2.5 ATP

Question 34

What is the main mechanism underlying mitochondrial dysfunction disorders?

Answer 34

Accumulation of ROS and mtDNA damage

Question 35

What is a cybrid? What is it useful in testing for?

Answer 35

Immortal cell de-mito’ed + denucleated patient fibroblast. If mito function normal, nuclear problem. If mito fxn abnormal, mito problem.