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Flashcards in ETC Deck (51):
1

ETC overview

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

2

redox reactions in biological systems

represent transfer of H atoms

3

mitochondria: outer membrane

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

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mitochondria: inner membrane

impermeabel to most small ions, small and large molecules

5

mitochondria: matrix

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

6

mitochondria

transcriptional and translational machinery

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complexes imbedded in the inner membrane

complexes I, II, III, IV, V
-spans the whole membrane from side to side

8

Complex V

enzyme ATP-synthase

9

What is the only nonprotein carrier?

CoQ

10

complex I

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

11

complx II

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

12

CoQ

-ONLY nonprotein carrier
-quinine derivative with long hydrophobic tail

13

Complex III

-cyt b
-cty c1

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complex IV

-cyt a
-cyt a3

15

cyt c

freely moving in the inter membrane space

16

Cyt iron

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

17

Complex IV

-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

18

Transfer of e- down the ETC

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

19

oxidative phosphorylation: the chemiosmotic hypothesis

-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

20

Complex V

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

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ATP-synthase function

-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

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inhibition of ETC

-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

23

Complex 1 inhibitor: amytal

-barbiturate
-proper drug usage

24

Complex I inhibitor: rotenon

used as an insecticide, piscicide, and pesticide

25

Complex III inhibitor: antimycin A

piscicide

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Complex IV inhibitor: cyanide (CN-)

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

27

Complex IV inhibitor: CO2

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

28

Complex IV inhibitor: sodium azide (NaN3)

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

29

Complex V inhibitor: Oligomycin

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

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coupling in normal mitochondria

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

31

uncoupling

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

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uncoupling: naturally

UCPs localized in the inner mitochondrial membrane

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synthetic uncouplers

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

34

UCPs

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

35

UCP1 (thermogenin)

found in brown adipose tissue of mammals

36

UCP2, 3, 4, and 5

found in other tissues but function not understood

37

2,4-dinitrophenol

-synthetic uncoupler
-weight loss drug
-fatal hyperthermia

38

salicylic acid

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

39

Reactive Oxygen Species (ROS)

-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

40

mtDNA

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

41

Leber Hereditary Optic Neuropathy (LHON)

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

42

mitochondrial in apoptosis

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

43

iron deficiency

-several proteins in the ETC require iron
-tiredness

44

Leber hereditary optic neuropathy (LHON)

optic neuropathy
optic atrophy

45

Neurogenic muscle weakenss ataxia retinitis pigmentosa (NARP)

retinal dystrophy
cone or cone-rod dystrophy

46

Maternally inherited Leigh disease (MILS)

RPE dystrophy
Optic Atrophy

47

Mitochondrial encephalopathy lactic acidosis stroke like episodes (MELAS)

maculopathy
Cone-Rod dystrophy
Hemianopsia

48

Maternally inherited diabetes and deafness (MIDD)

pattern maculopathy
pigmentary retinopathy

49

Myoclonic epilepsy ragged red fibers (MERRF)

Optic atrophy
Mild pigmentary retinopathy

50

Kearns-Sayre Syndrome (KSS)

Pigmentary retinopathy
strabismus ptosis

51

Chronic progressive extraocular ophthalmoplegia (CPEO)

Ptosis
Strabismus
Ophthalmoplegia