ETC Flashcards

1
Q

ETC overview

A

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

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2
Q

redox reactions in biological systems

A

represent transfer of H atoms

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3
Q

mitochondria: outer membrane

A

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

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4
Q

mitochondria: inner membrane

A

impermeabel to most small ions, small and large molecules

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5
Q

mitochondria: matrix

A
  • TCA cycle enzymes
  • FA oxidation enzymes
  • mtDNA and mtRNA
  • mitochondrial ribosomes
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6
Q

mitochondria

A

transcriptional and translational machinery

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7
Q

complexes imbedded in the inner membrane

A

complexes I, II, III, IV, V

-spans the whole membrane from side to side

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8
Q

Complex V

A

enzyme ATP-synthase

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9
Q

What is the only nonprotein carrier?

A

CoQ

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10
Q

complex I

A
  • NADH dehydrogenase
  • accepts e- from glycolysis, TCA
  • FMN, accepts H atoms to make FMNH2
  • iron sulfur center
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11
Q

complx II

A
  • succinate dehydrogenase
  • the only TCA enzyme embedded in the inner mitochondrial membrane
  • FAD contains iron sulfur center
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12
Q

CoQ

A
  • ONLY nonprotein carrier

- quinine derivative with long hydrophobic tail

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13
Q

Complex III

A
  • cyt b

- cty c1

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14
Q

complex IV

A
  • cyt a

- cyt a3

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15
Q

cyt c

A

freely moving in the inter membrane space

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16
Q

Cyt iron

A

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

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17
Q

Complex IV

A
  • 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
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18
Q

Transfer of e- down the ETC

A

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

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19
Q

oxidative phosphorylation: the chemiosmotic hypothesis

A
  • 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
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20
Q

Complex V

A
  • 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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21
Q

ATP-synthase function

A
  • 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
22
Q

inhibition of ETC

A
  • 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
Q

Complex 1 inhibitor: amytal

A
  • barbiturate

- proper drug usage

24
Q

Complex I inhibitor: rotenon

A

used as an insecticide, piscicide, and pesticide

25
Q

Complex III inhibitor: antimycin A

A

piscicide

26
Q

Complex IV inhibitor: cyanide (CN-)

A
  • irreversibly binds to the Fe3+ in the heme group of Cyt C-oxidase
  • house fires
27
Q

Complex IV inhibitor: CO2

A

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

28
Q

Complex IV inhibitor: sodium azide (NaN3)

A

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

29
Q

Complex V inhibitor: Oligomycin

A

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

30
Q

coupling in normal mitochondria

A

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

31
Q

uncoupling

A

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

32
Q

uncoupling: naturally

A

UCPs localized in the inner mitochondrial membrane

33
Q

synthetic uncouplers

A

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

34
Q

UCPs

A
  • allow H+ to flow back into matrix

- free energy released as heat (non shivering thermogenesis)

35
Q

UCP1 (thermogenin)

A

found in brown adipose tissue of mammals

36
Q

UCP2, 3, 4, and 5

A

found in other tissues but function not understood

37
Q

2,4-dinitrophenol

A
  • synthetic uncoupler
  • weight loss drug
  • fatal hyperthermia
38
Q

salicylic acid

A
  • causes uncoupling
  • aspirin
  • overdoses will cause high fever, profuse sweating, and can be fatal
39
Q

Reactive Oxygen Species (ROS)

A
  • 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
Q

mtDNA

A
  • encodes 12 of 120 proteins
  • constant exposure to ROS
  • oxidative defects in oxidative phosphorylation
  • severly affect highly aerobic tissues
41
Q

Leber Hereditary Optic Neuropathy (LHON)

A

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

42
Q

mitochondrial in apoptosis

A
  • intrinsic
  • pores
  • allow Cyt C to be released
  • caspases (proteolytic enzymes)
  • cause cleavage of key proteins
43
Q

iron deficiency

A
  • several proteins in the ETC require iron

- tiredness

44
Q

Leber hereditary optic neuropathy (LHON)

A

optic neuropathy

optic atrophy

45
Q

Neurogenic muscle weakenss ataxia retinitis pigmentosa (NARP)

A

retinal dystrophy

cone or cone-rod dystrophy

46
Q

Maternally inherited Leigh disease (MILS)

A

RPE dystrophy

Optic Atrophy

47
Q

Mitochondrial encephalopathy lactic acidosis stroke like episodes (MELAS)

A

maculopathy
Cone-Rod dystrophy
Hemianopsia

48
Q

Maternally inherited diabetes and deafness (MIDD)

A

pattern maculopathy

pigmentary retinopathy

49
Q

Myoclonic epilepsy ragged red fibers (MERRF)

A

Optic atrophy

Mild pigmentary retinopathy

50
Q

Kearns-Sayre Syndrome (KSS)

A

Pigmentary retinopathy

strabismus ptosis

51
Q

Chronic progressive extraocular ophthalmoplegia (CPEO)

A

Ptosis
Strabismus
Ophthalmoplegia