ETC

Question 1

ETC overview

Answer 1

the oxidation reactions are coupled to the transfer of e- (reduction) to the e- carriers NAD+ and FAD (oxidized)

Question 2

redox reactions in biological systems

Answer 2

represent transfer of H atoms

Question 3

mitochondria: outer membrane

Answer 3

permeabel to most ions and small molecules via small channels, porins

Question 4

mitochondria: inner membrane

Answer 4

impermeabel to most small ions, small and large molecules

Question 5

mitochondria: matrix

Answer 5

• TCA cycle enzymes
• FA oxidation enzymes
• mtDNA and mtRNA
• mitochondrial ribosomes

Question 6

mitochondria

Answer 6

transcriptional and translational machinery

Question 7

complexes imbedded in the inner membrane

Answer 7

complexes I, II, III, IV, V

-spans the whole membrane from side to side

Question 8

Complex V

Answer 8

enzyme ATP-synthase

Question 9

What is the only nonprotein carrier?

Answer 9

CoQ

Question 10

complex I

Answer 10

• NADH dehydrogenase
• accepts e- from glycolysis, TCA
• FMN, accepts H atoms to make FMNH2
• iron sulfur center

Question 11

complx II

Answer 11

• succinate dehydrogenase
• the only TCA enzyme embedded in the inner mitochondrial membrane
• FAD contains iron sulfur center

Question 12

CoQ

Answer 12

• ONLY nonprotein carrier

- quinine derivative with long hydrophobic tail

Question 13

Complex III

Answer 13

• cyt b

- cty c1

Question 14

complex IV

Answer 14

• cyt a

- cyt a3

Question 15

cyt c

Answer 15

freely moving in the inter membrane space

Question 16

Cyt iron

Answer 16

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

Question 17

Complex IV

Answer 17

• cyt a+a3 or cytochrome c oxidase
• Cu required for e- transport
• only complex in which the heme Fe has a site that directly reacts with O2
• e- moves from Cua to Cyt a3

Question 18

Transfer of e- down the ETC

Answer 18

driven because NADH is a strong electron do not, and O2 is a strong electron acceptor

Question 19

oxidative phosphorylation: the chemiosmotic hypothesis

Answer 19

• electrical gradient
• pH gradient
• this energy created by this used to drive ATP synthesis
• proton gradient serves as common intermediate that couples oxidation to phosphorylation

Question 20

Complex V

Answer 20

• ATP-synthase
• multisubunit enzyme
• domain Fo spans the inner mitochondrial membrane
• domain F1-extramembranous that appears as a sphere that protrudes into the matrix

Question 21

ATP-synthase function

Answer 21

• protons flow back through Fo, driven by gradient, which drives rotation of F1 domain
• rotation of F1 causes conformational change that allow it to bind ATP +Pi, and phosphorylate ADP to ATP and release ATP

Question 22

inhibition of ETC

Answer 22

• blocking e- transfer by any one of these inhibitors stops electron flow from substrate to O2 because the reactions of ETC are tightly coupled like meshed gears
• lactate build up, highly aerobic tissues affected

Question 23

Complex 1 inhibitor: amytal

Answer 23

• barbiturate

- proper drug usage

Question 24

Complex I inhibitor: rotenon

Answer 24

used as an insecticide, piscicide, and pesticide

Question 25

Complex III inhibitor: antimycin A

Answer 25

piscicide

Question 26

Complex IV inhibitor: cyanide (CN-)

Answer 26

- irreversibly binds to the Fe3+ in the heme group of Cyt C-oxidase - house fires

Question 27

Complex IV inhibitor: CO2

Answer 27

-binds irreversibly however the primary toxicity is associated with the tight binding to hemoglobin

Question 28

Complex IV inhibitor: sodium azide (NaN3)

Answer 28

-binds similarly to cyanide to the Fe3+ of iron in cytochrome. propellant in airbags, explosives, in lab as antimicrobial perservative

Question 29

Complex V inhibitor: Oligomycin

Answer 29

binds to the Fo domain closing the proton channel leading back into the matrix, shutting down ATP synthesis. a tool to study ATP in the lab

Question 30

coupling in normal mitochondria

Answer 30

ATP synthesis is coupled to e- transport through the H+ gradient

Question 31

uncoupling

Answer 31

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

Question 32

uncoupling: naturally

Answer 32

UCPs localized in the inner mitochondrial membrane

Question 33

synthetic uncouplers

Answer 33

nonprotein compounds that increase he permeability of the inner mitochondrial membrane to H+

Question 34

UCPs

Answer 34

- allow H+ to flow back into matrix | - free energy released as heat (non shivering thermogenesis)

Question 35

UCP1 (thermogenin)

Answer 35

found in brown adipose tissue of mammals

Question 36

UCP2, 3, 4, and 5

Answer 36

found in other tissues but function not understood

Question 37

2,4-dinitrophenol

Answer 37

- synthetic uncoupler - weight loss drug - fatal hyperthermia

Question 38

salicylic acid

Answer 38

- causes uncoupling - aspirin - overdoses will cause high fever, profuse sweating, and can be fatal

Question 39

Reactive Oxygen Species (ROS)

Answer 39

- unavoidable by product of ETC - incomplete reduction of oxygen to water - can damage proteins, lipids, DNA, RNA, etc, present in mitochondria - can increase production of free radicals

Question 40

mtDNA

Answer 40

- encodes 12 of 120 proteins - constant exposure to ROS - oxidative defects in oxidative phosphorylation - severly affect highly aerobic tissues

Question 41

Leber Hereditary Optic Neuropathy (LHON)

Answer 41

MERRF, and MELAS. Leigh syndrome can result from mutations in tDNA or nuclear DNA

Question 42

mitochondrial in apoptosis

Answer 42

- intrinsic - pores - allow Cyt C to be released - caspases (proteolytic enzymes) - cause cleavage of key proteins

Question 43

iron deficiency

Answer 43

- several proteins in the ETC require iron | - tiredness

Question 44

Leber hereditary optic neuropathy (LHON)

Answer 44

optic neuropathy | optic atrophy

Question 45

Neurogenic muscle weakenss ataxia retinitis pigmentosa (NARP)

Answer 45

retinal dystrophy | cone or cone-rod dystrophy

Question 46

Maternally inherited Leigh disease (MILS)

Answer 46

RPE dystrophy | Optic Atrophy

Question 47

Mitochondrial encephalopathy lactic acidosis stroke like episodes (MELAS)

Answer 47

maculopathy Cone-Rod dystrophy Hemianopsia

Question 48

Maternally inherited diabetes and deafness (MIDD)

Answer 48

pattern maculopathy | pigmentary retinopathy

Question 49

Myoclonic epilepsy ragged red fibers (MERRF)

Answer 49

Optic atrophy | Mild pigmentary retinopathy

Question 50

Kearns-Sayre Syndrome (KSS)

Answer 50

Pigmentary retinopathy | strabismus ptosis

Question 51

Chronic progressive extraocular ophthalmoplegia (CPEO)

Answer 51

Ptosis Strabismus Ophthalmoplegia