ETC Flashcards

1
Q

ETC overview

A
  • energy rich molecules are metabolized by series of oxidation reactions yielding CO2 and H2O
  • oxidation reactions are coupled to the transfer or electrons(reduction) to the electron carriers FAD and NAD+(oxidation)
  • carriers donate electron to ETC and lose free eneegy
  • electron is coupled with proton to create gradient
  • flow of protons drives ATP synthase
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2
Q

RedOx chemical reactions

A

-represent transfer of H atoms (1 proton and 1 electron)

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3
Q

Mitochondria outer membrane

A

-permeable to most ions and small molecules

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4
Q

Mitochondria inner membrane

A

-impermeable to most small ions and small and large molecules

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5
Q

Mitochondrial matrix

A
  • TCA cycle enzymes (except complex 2)
  • fatty acid oxidation enzymes
  • mtDNA and mtRNA (circular and encode for some things involved in ETC)
  • mitochondrial ribosomes
  • ETC takes place here
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6
Q

protein complexes

A
  • embedded in the inner membrane and span the WHOLE membrane.
  • complexes 1-4 are part of the electron transprt
  • complex 5 is the enzyme ATP-synthase
  • CoQ is the only nonprotein carrier (hydrophobic and can freely move around the membrane)
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7
Q

Complex 1

A
  • NADH dehydrogenase
  • accepts electron from NADH generated during glycolysis, pyruvate decarboxylation, and TCA cycle
  • contains FMN that accepts 2 hydrogen atoms
  • contains iron sulfur center required for next step
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8
Q

Complex 2

A
  • succinate dehydrogenase
  • ONLY ONE embedded in inner mitochondrial membrane
  • FAD contains iron sulfur center
  • FADH2 generated are directly transferred to CoQ and skip complex 1
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9
Q

Coenzyme Q

A
  • only non protein carrier
  • quinine derivative with long hydrophobic tail so it can freely move along membrane
  • accepts the electron from complex 1 and 2 and pass them to complex 3
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10
Q

Cytochrome proteins

A
  • CYT
  • Cyt b and c1=complex 3
  • Cyt a and a3=complex 4
  • Cyt c freely moves in intermembrane space because soluble
  • each contain heme group
  • Cyt iron is reversibly converted from ferric(Fe3+) to ferrous(Fe2+)
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11
Q

Complex 4

A
  • Cyt a and a3 or c oxidase
  • contains copper required for electron transfer
  • the only complex that contains heme iron group that directly interacts with O2
  • electron moves from CuA to Cyta3 associated with Cub to O2
  • oxygen is last acceptor because it is the strongest
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12
Q

Strongest donor and acceptor

A
  • NADH is strongest donor

- O2 is strongest acceptor so held for last so you can continue to transfer electrons down the chain

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13
Q

Chemiosmotic hypothesis

A
  • as electrons go through 1,3,4, the reaction is coupled with pumping of protons across inner mitochondrial membrane to intermembrane space
  • creates electrical and pH gradient(outside is more positive)
  • gradient drives ATP synthesis
  • gradient serves as common intermediate that couples oxidation to phosphorylation
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14
Q

Complex 5

A
  • ATP-Synthase
  • multisubunit enzyme
  • domain F0-spans mitochondrial membrane
  • domain F1- is extramembranous(in mitochondrial matrix)(head spear is in matrix)
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15
Q

ATP-Synthase Function

A
  • protons flow back through F0 domain driven by the gradient
  • F1 domain rotates
  • F1 goes through conformational changes that allow ATP+P to bind and phosphorylate ADP—>ADP, and release ATP
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16
Q

Inhibition of ETC

A
  • prevent the flow of electrons
  • results in NADH build up
  • build up inhibits TCA cycle and causes pyruvate to go to lactate
  • serum lactate levels elevate
  • highly aerobic tissues are effected(heart and brain)

-any inhibition will stop the whole damn thing

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17
Q

Inhibition of Complex 1

A

Amytal- a barbiturate, okay to take medication if correct dosage
Rotenone- insecticide, piscicide, and pesticide

18
Q

Inhibition of Complex 3

A

Antimycin A(piscicide

19
Q

CN Inhibition of Complex 4

A

Cyanide-irreversibly binds to ferric in the heme group of Cyt C-oxidase
-seen in people exposed to fires

20
Q

CO inhibition of Complex 4

A

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

21
Q

NaN3 inhibition of Complex 4

A
  • binds to ferris in cytochromes
  • used as propellant in air bags and explosives
  • used as antimicrobial preservatives
22
Q

Inhibition of Complex 5

A

Oligomycin- binds fo F0 domain and closes the proton channel leading back to the matrix and shuts down ATP synthesis
-used to study ETC in labs

23
Q

Coupling in normal mitochondria

A
  • ATO synthesis is coupled to electron transport through the proton grandient
  • change in one has the same effect on the other
24
Q

Uncoupling

A

-allowing protons to flow back through the membrane without generation of ATP
Natural- UCP’s localized in mitochondrial membrane (creates protein leak)
Synthetic- non protein compounds that increase permeability of the inner mitochondrial membrane to protons

25
Q

Uncoupling proteins

A

-allow proton to go back to the matrix by skipping complex 5 and not generating ATP

26
Q

Nonshivering thermogenesis

A

-free energy released as heat by UCP

27
Q

UCP1

A
  • thermogin

- found in brown fat

28
Q

UCP2,3,4,5

A
  • have been found in other tissues(heart, muscle, liver) but their function is not known
  • tissue specific
29
Q

2,4-dinitrophenol

A
  • weight loss in 1930
  • easy to overdose
  • fatal hypothermia
30
Q

Salicylic acid

A
  • can cause uncoupling
  • aspirin
  • high fever/sweating/fatal overdose
31
Q

Reactive oxygen species

A
  • incomplete reduction of oxygen to water causes production of ROS
  • O2-, H2O2, OH radicals
  • unavoidable product of ETC
  • potential to damage things in mitochondria
  • damage/mutations in ETC components can increase production of free radicals
32
Q

mtDNA

A
  • encodes 13 of 120 proteins required for oxidative phosphorylation
  • high mutation rate due to ROS
  • mutations of oxidative phosphorylation highly affect aerobic tissues
33
Q

Apoptosis

A
  • programmed cell death
  • initiated through mitochondrial intrinsic pathways resulting in the formation of pores in the outer membrane
  • pores allow Cyt c to be released into the cytosol
  • Cyt-c can interact and activate proteolytic enzymes(caspases)
  • caspases cause cleavage of proteins that change characteristics and result in apoptosis
34
Q

Iron level deficiency

A
  • several proteins in ETC require Iron

- low levels may result in tiredness and iron deficiency anemia

35
Q

LHON

A
  • leber hereditary optic neuropathy

- optic neuropathy and optic atrophy

36
Q

NARP

A
  • Neruological muscle weakness, Ataxia, Retinitis pigmentosa

- retinal dystrophy, cone dystrophy

37
Q

MILS

A
  • Maternally inherited Leigh disease

- RPE dystrophy, optic atrophy

38
Q

MELAS

A
  • Mitochondrial encephalopathy, lactic acidosis, stroke like episodes
  • Maculopathy, cone-rod dystrophy, hemianopsia
39
Q

MIDD

A

Maternally inherited diabetes and deafness

-Pattern maculopathy, pigmentary retinopathy

40
Q

MERRF

A

Myoclonic epilepsy, ragged red fibers

-optic atrophy, mild pigmentary retinopathy

41
Q

KSS

A

Kearns-sayre Syndrome

-Pigmetary retinopathy, strabismus ptosis

42
Q

CPEO

A

chronic progressive extraocular ophthalmoplegia

-ptosis, strabismus, ophthalmoplegia