Electron Transport Chain

Question 1

What are the biological election carriers?

Answer 1

Cofactors NAD+ and FAD

Question 2

Glucose catabolism is a series of ______ ______ ______

Answer 2

Redox chemical reactions

Question 3

Redox chemical reactions in biological systems represent what?

Answer 3

The transfer of H atoms (1p+ and 1e-)

Question 4

NAD+ is ______ and NADH is ______

Answer 4

Oxidized, reduced

Question 5

FAD is _____ and FADH2 is ______

Answer 5

Oxidized, reduced

Question 6

Mitochondria outer membrane:

Answer 6

Permeable to most ions and small molecules via channels and porins

Question 7

Inner membrane of mitochondria

Answer 7

Impermeable to most small ions, small and large molecules

Question 8

Mitochondrial matrix contains:

Answer 8

TCA cycle enzymes, fatty acid oxidation enzymes, mtDNA, mtRNA, and mitochondrial ribosomes

Question 9

ETC takes place in the:

Answer 9

Mitochondrial inner and outer membrane

Question 10

5 protein complexes in inner membrane

Answer 10

Complex I, II, III, IV, V

Question 11

Complex V is the…

Answer 11

ATP-synthase

Question 12

What is the only non protein carrier or the ETC?

Answer 12

CoQ

Question 13

Complex I

Answer 13

NADH dehydrogenase

Accepts e- from NADH

Contains FMN (similar to FAD) that accepts H atoms to make FMNH2

Contains an Iron Sulfur center that is required for next transfer

Question 14

Complex II

Answer 14

Succinate dehydrogenase

Only TCA enzyme embedded in inner mitochondrial membrane

FAD contains iron-sulphur center

FADH2 generated are directly transferred to CoQ bypassing Complex I

Question 15

CoQ

Answer 15

Ubiquinone

Only nonprotein carrier

Accepts e- from Complex I and II and passes them to Complex III

Question 16

Ubiquinone

Answer 16

Quinine derivative with long hydrophobic tail (free moving within the membrane)

Question 17

What is the only TCA enzyme embedded in the inner mitochondrial membrane?

Answer 17

Succinate dehydrogenase, Complex II

Question 18

Cytochrome proteins in ETC

Answer 18

In Complex III

Cyt b, cyt c1

In Complex IV

Cyt a, cyt a3

Cyt c-freely moving in the intermembrane space

Question 19

What is the only freely moving cytochrome protein in ETC?

Answer 19

Cytochrome C

Question 20

Each cytochrome contains a ….

Answer 20

Heme group (porphyrin ring + iron)

Question 21

What’s so special about the Cytochrome iron?

Answer 21

It is reversibly converted from ferric (Fe3+) to ferrous (Fe2+) form

During normal function of electron acceptor/donor

Question 22

Complex IV

Answer 22

Contains copper required for e- transfer

Only complex in which the heme Fe has a site that directly interacts with O2

E- move from CuA to Cyta3 associated with CuB to O2

Question 23

What drives the transfer of e- down the ETC?

Answer 23

NADH because it is a strong electron donor

O2 because it’s a strong electron acceptor

Question 24

What is the only complex in which the heme has a site that directly reacts with O2?

Answer 24

Complex IV

Question 25

The Chemiosmotic Hypothesis

Answer 25

As electrons are transported through Complexes I, III, IV the reaction is coupled to the pumping of protons across the inner mitochondrial membrane to the intermembrane space Creates electrical gradient (outside more positive) and a pH gradient (outside lower) Used to drive ATP synthesis

Question 26

Complex V

Answer 26

ATP Synthase Multisubunit enzyme Domain Fo- spans the inner mitochondrial membrane Domain F1- extra membranous that appears as a sphere that protrudes into the mitochondrial matrix

Question 27

Function of ATP synthase:

Answer 27

Protons flow back through the Fo domain driven by the gradient (which drives the F1 domain) Rotation Fo the F1 domain causes conformational changes that allow it to: bind ADP + Pi Phosphorylate ADP to ATP release ATP

Question 28

Inhibition of the ETC

Answer 28

- prevents flow of e- through ETC - results in NADH buildup - inhibits TCA cycle (causes anaerobic Pyruvate reduction to lactate) - serum lactate builds up - highly aerobic tissues (heart, brain) will be effected most severely

Question 29

If the ETC is inhibited, and the TCA cycle is inhibited due to NADH buildup, what happens?

Answer 29

Anaerobic Pyruvate reduction to lactate

Question 30

Which tissues are most affected by inhibition of ETC?

Answer 30

Heart and brain, highly aerobic tissues

Question 31

Inhibitors of Complex I

Answer 31

Amytal: barbiturate Rotenone: used as insecticide, piscicide, and pesticide

Question 32

Inhibitor of Complex III

Answer 32

Antimycin A: used as piscicide

Question 33

Inhibitors of Complex IV:

Answer 33

Cyanide (CN-) Irreversibly binds to Fe3+ in the heme group of Cyt C-oxidase May be see clinically from people exposed to house fires or industrial fires (from burning polyurethane found in foam mattresses and furniture) CO -binds irreversibly however the primary toxicity is associated with the tight binding to hemoglobin sodium azide (NaN3) - binds similar to CN to Fe3+ in cytochromes. Used as propellant in airbags, explosives, and as antimicrobial preservative

Question 34

Inhibitor in Complex V

Answer 34

Oligomycin - binds to Fo domain Closes proton channel leading back into the matrix, and shutting down ATP synthesis A tool to study ETC in lab

Question 35

Uncoupling in the ETC

Answer 35

Allowing H+ to flow back through the membrane without generation of ATP

Question 36

Naturally Uncoupling in ETC

Answer 36

Uncoupling proteins (UCPs) localized in the inner mitochondrial membrane

Question 37

Synthetic uncouplers in ETC

Answer 37

Compounds, nonprotein, that increase the permeability of the inner mitochondrial membrane to H+

Question 38

forms of UCPs

Answer 38

UCP1- thermogenin, found in brown adipose tissue UCP2, UCP3, UCP4, UCP5 - found in muscle, heart, liver, function not understood

Question 39

Synthetic uncouplers in ETC

Answer 39

2,4-dinitrophenol Used as weight loss drug in 30's Banned because easy to OD compounds containing Salicylic Acid (aspirin) -can be fatal

Question 40

Reactive Oxygen Species in ETC

Answer 40

ROS Superoxide (O2-), hydrogen peroxide (H2O2), and hydroxyl radicals (OH) **produced by incomplete reduction of Oxygen to water Unavoidable byproduct of ETC Damage to proteins, lipids, DNA, RNA etc

Question 41

mtDNA

Answer 41

Encodes 13 of 120 proteins required for oxidative phosphorylation Has a high mutation rate compared to nuclear DNA --due to constant exposure to ROS Mutations cause oxidative defects in ox phos Severely affect high aerobic tissues

Question 42

Programmed cell death

Answer 42

Apoptosis

Question 43

Apoptosis and Mitochondria

Answer 43

Apoptosis is initiated though mitochondrial intrinsic pathways resulting in formation of pores in outer mito.membrane Pores then allow CytC to be released into cytosol CytC then interacts with pro-apoptotic factors to activate a family of proteolytic enzymes (caspases) Caspases then cause cleavage of key proteins that result in the morphological and biochemical changes characteristic of apoptosis

Question 44

What is a caspase?

Answer 44

Family of proteolytic enzymes that can cause apoptosis via cleavage of proteins

Question 45

Iron deficiency anemia and ETC function

Answer 45

Several proteins in ETC require iron. Insufficient iron levels may cause come of the tiredness associated with iron deficiency anemia because of the affects on ETC