ELECTRON TRANSPORT CHAIN 4 COMPLEXES OF RESPIRATORY CHAIN

BIOMEDICAL IMPORTANCE o Complex II (Succinate-Q Reductase)

- Complex wherein substrates with more positive
o Oxidative Phosphorylation redox potential than NAD pass electrons to Q
- Process wherein respiration is coupled to the o Complex III (Q-Cytochrome C Oxidoreductase)
generation of ATP - Passes electrons to cytochrome C
SPECIFIC ENZYMES AND THEIR LOCATION IN MITO o Complex IV (Cytochrome C oxidase)
- Completes the chain, passing the electrons to O2
o Mitochondrial matrix is enclosed by a double causing it to be reduced to H20
membrane o The 4 complexes are embedded in the inner
 Outer Membrane mitochondrial membrane
- Permeable to most metabolites  Ubiquinone and cytochrome C are mobile
 Enzymes:  Ubiquinone
 Acyl-CoA Synthetase - Rapidly diffuses within the membrane
 Glycerol Phosphate Acyltransferase  Cytochrome C
 Inner Membrane - Soluble protein
- Selectively permeable
 Enzymes: Flavoproteins and Iron-Sulfur Proteins
 Respiratory Chain o Flavoproteins
 ATP Synthase - Important components of complex I and II
 Membrane Transporters
 FMN/FAD
 Intermembrane Space
- Can be reduced in reactions involving the
 Enzymes:
 Creatine Kinase transfer of two electrons
 Adenylyl Kinase o Iron-Sulfur Proteins (Fe-S)
- Important components of complex I, II and III
RESPIRATORY CHAIN AS A PROTON PUMP - Take part in single electron transfer reaction in
o Reducing Equivalents which one Fe atom undergoes oxidoreduction
- H or electrons used during the ETC between Fe2 and Fe3
o Enzymes of the following are all found in the
Complex I
mitochondria:
 Kreb’s Cycle o Complex I
 Beta Oxidation - Large L-shaped multisubunit protein that
 Respiratory Chain Complexes catalyzes electron transfer from NADH to Q
 Oxidative Phosphorylation - 4 H+ are transferred across the matrix to the
o Respiratory Chain intermembrane space during the process
- Collects and transports reducing equivalents
directing them to their final reaction with oxygen
to form water o Electrons flow
o Oxidative Phosphorylation
 NADH > FMN > Fe-S Centers > Q
- Process by which the liberated free energy is
trapped as high energy phosphate Complex II
4 Complexes of the Respiratory Chain o FADH2
o Electrons flow through the respiratory chain - Formed during the conversion of succinate to
through a redox span of 1.1v from NAD+/NADH to fumarate in the citric acid cycle
O2/2H2O o Electron Flow
o Complex I (NADH-Q Oxidoreductase)  FADH2 > Fe-s centers > Q
- Electrons are transferred from NADH to
coenzyme Q (ubiquinone)
ELECTRON TRANSPORT CHAIN Complex III
Complex III
o Complex III
- Passes electrons from QH2 to cytochrome c
o Process involves:
 Cytochrome c1 Complex IV
 Cytochrome bL
 Cytochrome bH o Complex IV
 Rieske Fe-S - Oxidizes reduced cytochrome C with the
- Unusual Fe-s in which one Fe atom is linked concomitant reduction of O2 to 2 molecules of
to 2 histidine residues rather than cysteine water
o Q Cycle
 3 Forms of Q:
 Oxidized Quinone
 Reduced Quinone
o 4 electrons are transferred from cytochrome c to O2
 Semiquinone
via two heme groups a and a3, and Cu
- Formed transiently during the cycle
o Electron Flow:
 Result of 1 turn of Q cycle:
 Oxidation of 2QH2 to Q  CuA > heme a > heme a3 > CuB > O2
- Releases 4H to the intermembrane space  CuA
 Reduction of Q to QH2 - Contains 2 Cu atoms linked to two protein
- Causes take up of 2H from the matrix cysteine SH groups
o Q – carries 2 electrons, while Cytochrome – carries o 8 H+ are removed from the matrix
one electron  4H used to form 2H2O
- Oxidation of 1 QH2 is coupled to the reduction of  4H pumped into intermembrane space
2 molecules of cytochrome c o For every pair of electrons passing down the chain
from NADH or FADH2:
 2H are pumped across the membrane by
complex IV
 O2 remains tightly bound to Complex IV until it
is fully reduced

ELECTRON TRANSPORT VIA RESPIRATORY CHAIN

o Oxidative Phosphorylation
- Flow of electrons through respiratory chain that
generates ATP
o Chemiosmotic Theory
- Two processes are coupled by a proton gradient
across the inner mitochondrial membrane
- The proton motive force caused by the
electrochemical potential difference drive the
mechanism of ATP synthesis

ATP SYNTHASE

o ATP Synthase
- Membrane located structure which is driven by
PMF that forms ATP in the presence of PI + ADP
- Embedded in the inner membrane
ELECTRON TRANSPORT CHAIN o For each NADH oxidized:
 Complex I and III = 4 protons
ATP SYNTHASE
 Complex IV = 2 protons
o Structure of ATP Synthase:
RESPIRATORY CHAIN INHIBITORS
 F1
- Protein that forms ball-like shape arranged o Complex I Inhibitors:
around an axis composed of several subunits  Barbiturates
- Projects into the matrix and contains the - Inhibit electron transport by blocking the
phosphorylation mechanism transfer from Fe-S to Q
 F0 o Complex II
- Spans the membrane and forms a proton  Malonate
channel o Complex III
 Antimycin A
 Dimercaprol
o Complex IV
 H2S
 Carbon Monoxide
 Cyanide
o ATP Synthase
 Atractyloside
- Inhibits oxidative phosphorylation by
inhibiting the transporter of ADP into ATP
out of mitochondrion
 Oligomycin
- Completely blocks oxidation and
phosphorylation by blocking the flow of
electrons through ATP synthase
o Mechanism:
o Uncouplers
 Protons flowing through F0 driven by the
- Dissociate oxidation in the respiratory chain from
proton gradient, drives the production of ATP in
phosphorylation
the F1 complex
- Toxic, causing respiration to become
 Binding Change Mechanism
uncontrolled since the rate is no longer limited
- Conformation of the beta subunits in F1 is
by ADP or Pi concentration
changed as the axis rotates from one that
 2,4-dinitrophenol
binds ATP tightly to one that releases ATP
- Most used uncoupler
and binds ADP and Pi so that the next ATP is
formed  Thermogenin
- Found in brown adipose tissue that functions
to generate body heat for newborn babies