Electron Transport Chain Flashcards

1
Q

What are the biological election carriers?

A

Cofactors NAD+ and FAD

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2
Q

Glucose catabolism is a series of ______ ______ ______

A

Redox chemical reactions

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3
Q

Redox chemical reactions in biological systems represent what?

A

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

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4
Q

NAD+ is ______ and NADH is ______

A

Oxidized, reduced

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5
Q

FAD is _____ and FADH2 is ______

A

Oxidized, reduced

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6
Q

Mitochondria outer membrane:

A

Permeable to most ions and small molecules via channels and porins

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7
Q

Inner membrane of mitochondria

A

Impermeable to most small ions, small and large molecules

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8
Q

Mitochondrial matrix contains:

A

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

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9
Q

ETC takes place in the:

A

Mitochondrial inner and outer membrane

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10
Q

5 protein complexes in inner membrane

A

Complex I, II, III, IV, V

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11
Q

Complex V is the…

A

ATP-synthase

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12
Q

What is the only non protein carrier or the ETC?

A

CoQ

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13
Q

Complex I

A

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

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14
Q

Complex II

A

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

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15
Q

CoQ

A

Ubiquinone

Only nonprotein carrier

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

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16
Q

Ubiquinone

A

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

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17
Q

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

A

Succinate dehydrogenase, Complex II

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18
Q

Cytochrome proteins in ETC

A

In Complex III

Cyt b, cyt c1

In Complex IV

Cyt a, cyt a3

Cyt c-freely moving in the intermembrane space

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19
Q

What is the only freely moving cytochrome protein in ETC?

A

Cytochrome C

20
Q

Each cytochrome contains a ….

A

Heme group (porphyrin ring + iron)

21
Q

What’s so special about the Cytochrome iron?

A

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

During normal function of electron acceptor/donor

22
Q

Complex IV

A

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

23
Q

What drives the transfer of e- down the ETC?

A

NADH because it is a strong electron donor

O2 because it’s a strong electron acceptor

24
Q

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

A

Complex IV

25
Q

The Chemiosmotic Hypothesis

A

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

26
Q

Complex V

A

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

27
Q

Function of ATP synthase:

A

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

28
Q

Inhibition of the ETC

A
  • 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
29
Q

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

A

Anaerobic Pyruvate reduction to lactate

30
Q

Which tissues are most affected by inhibition of ETC?

A

Heart and brain, highly aerobic tissues

31
Q

Inhibitors of Complex I

A

Amytal: barbiturate

Rotenone: used as insecticide, piscicide, and pesticide

32
Q

Inhibitor of Complex III

A

Antimycin A: used as piscicide

33
Q

Inhibitors of Complex IV:

A

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

34
Q

Inhibitor in Complex V

A

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

35
Q

Uncoupling in the ETC

A

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

36
Q

Naturally Uncoupling in ETC

A

Uncoupling proteins (UCPs) localized in the inner mitochondrial membrane

37
Q

Synthetic uncouplers in ETC

A

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

38
Q

forms of UCPs

A

UCP1- thermogenin, found in brown adipose tissue

UCP2, UCP3, UCP4, UCP5 - found in muscle, heart, liver, function not understood

39
Q

Synthetic uncouplers in ETC

A

2,4-dinitrophenol
Used as weight loss drug in 30’s
Banned because easy to OD

compounds containing Salicylic Acid (aspirin)
-can be fatal

40
Q

Reactive Oxygen Species in ETC

A

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

41
Q

mtDNA

A

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

42
Q

Programmed cell death

A

Apoptosis

43
Q

Apoptosis and Mitochondria

A

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

44
Q

What is a caspase?

A

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

45
Q

Iron deficiency anemia and ETC function

A

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