Oxidative Phosphorylation I Flashcards
ATP can be made during glycolysis, in an anaerobic process, but the most important source of ATP synthesis is
-An aerobic process
Oxidative phosphorylation
Involves a series of oxidation/reduction reactions, beginning with the NADH and FADH2 produced in the citric acid (TCA) cycle and ending with the reduction of oxygen to water
Oxidative phosphorylation
The oxygen required for this process is transported to every tissue in the body by
Hemoglobin
The process of oxidative phosphorylation takes place in the
Mitochondria
Oxidative phosphorylation is unique in that it has a key step which forms a
Proton gradient across the membrane
Oxidative phosphorylation is also unique in using proteins made from which two genomes?
- ) Our nuclear genome
2. ) Small mitochondrial genome
Cyanide results in death because it inhibits
Oxidative phosphorylation
Accumulated defects in the process, through free radical damage or other causes, may be involved in aging and many common neurodegenerative diseases, such as
Alzheimers and Parkinson’s
The use and transfer of energy in biological systems, and it must follow the same thermodynamic principles that hold for all reactions
Bioenergetics
Some reactions give off energy, such as
Catabolic reactions
Some reactions consume energy, such as
Anabolic reactions
The free energy value when all of the reactants and products are present at 1M concentration, neutral pH, standard conditions
Standard Free Energy (Delta-Go)
Reaction goes spontaneously as written and will give off energy if
Delta G is negative
Reaction will not go spontaneously as written and energy must be added to the system if
Delta G is positive
The reaction is at equilibrium if
Delta G is zero
The delta-G values of subsequent reactions are
-reactions can be couple for spontaniety
Additive
Made using energy from catabolic reactions and is then used ot drive anabolic reactions
ATP
A relatively simple molecule: it has an adenine (nitrogenous base), attached to a ribose (5 carbon sugar), which is bound to a chain of three phosphate groups
ATP
How many high-energy phosphate bonds does ATP have?
2
Removal of the terminal phosphate gives ADP and gives off
delta-D = -7.3 kcal/mol
The high charge of the three phosphates in ATP produces electrostatic repulsion which is relieved when it is hydrolyzed to form
ADP
The existence of four possible resonance forms for the inorganic phosphate Pi products leads to
Resonance stabilization
ATP works by direct transfer of a phosphate group to
Another molecule
Acts as an essential link between energy producing and energy consuming processes
ATP
The energy from oxidation of compounds is conserved in
ATP
What is the average consumption of ATP per 24 hours in the average human?
40 kg
During strenuous exercise, the rate of ATP utilization can be as high as
0.5 kg/min
A typical lipid bilayer, which is permeable to small molecules, but not permeable to proteins and other large molecules
Outer mitochondrial membrane
The narrow space between the outer and inner membranes
Intermembrane space
Located in the intermembrane space
Apoptotic molecules
Has many infoldings known as cristae, which increases its surface area
Inner mitochondrial membrane
This inner membrane is a most unusual membrane, in having extremely high protein content and in being impermeable to
Small and large molecules
Even K+ ions, Ca++ ions, ATP, ADP, protons and OH- groups cannot diffuse through the
Inner mitochondrial membrane
This membrane is the site of the electron transport chain and the process of oxidative phosphorylation
Inner mitochondrial membrane
The ATP synthase molecules which directly synthesis the ATP from ADP and phosphate are embedded in
Inner mitochondrial membrane
The mitochondrial matrix is the site of the
TCA cycle and FA oxidation
There are also small circular mitochondrial DNA molecules (mtDNA) in the
Matrix
These mtDNA molecules code for 13 polypeptide chains, all of which involves in
Oxidative phosphorylation
This mtDNA also codes for
tRNA and rRNA molecules
The mitochondrial genome codes for just
13 proteins
In the inner mitochondrial membrane, the electron transport chain undergoes a series of successive
Oxidation and reduction reactions
These redox reactions generate energy used to form a proton gradient across the
Inner mitochondrial membrane
This proton gradient is dissipated through the ATP synthase and leads to the formation of
ATP
There are 5 large protein complexes in the inner mitochondrial membrane, called complexes
I-V
Complexes I, II. III. and IV are all part of the
Electron transport chain
These 4 complexes work together with
- ) The lipid soluble?
- ) The water soluble?
- ) Coenzyme Q
2. ) Cytochrome C
The electron transport chain is also known as the respiratory chain, because of its need for oxygen as the terminal acceptor of
Electrons
The ATP synthase (also known as ATPase) which uses the energy of the proton gradient to catalyze the formation of ATP
Complex V
What is an oxidation-reduction reaction?
OIL-RIG
The loss or gain of an electron may be accompanied by a
Proton
What are three forms of reduction?
- ) Reduction by gain of electron
- ) Reduction by gain of hydrogen atom
- ) Reduction by gain of hydride ion
The standard oxidation reduction potential Eo’ (Volts) is measure of the affinity for a compound to
Accept or Donate electrons
The more POSITIVE the standard potential, the higher the affinity for
Electrons (Reduction)
Tend to lose electrons and reduce other compounds (as they get oxidized)
Strong reducing agents
Such strong reducing agents have a
Low or negative Eo
Want to accept electrons and oxidize other compounds (as they get reduced); they have a high positive Eo
Strong oxidizing agents
What are two examples of strong reducing agents?
NADH and FADH2
What is an example of a strong oxidizing agent?
O2
Oxidation-reduction reactions give off energy, and the amount of energy released depends on the standard oxidation potentials of the
Oxidizing and reducing pairs
It is known that the transfer of 2 electrons from NADH through all the components of the electron transport chain leads to the formation of
3 ATP molecules
The standard free energy change for the formation of ATP from ADP and Pi is DGo =
7.3 kcal/mol
Electrons are transferred from the products of the TCA cycle, NADH and succinate, to O2 through
Complexes I - IV, Coenzyme Q,a nd cytochrome C
Complex I is an
NADH-CoQ oxidoreductase
Accepts electrons directly from NADH in the mitochondrial matrix
Complex I
Cannot accept electrons from NADH when it is on the intermembrane space side of the inner mitochondrial membrane
Complex I
NADH gets oxidized to NAD+ and is available for anotherround of the TCA cycle, while complex I gets
Reduced
The largest complex in the electron transport chain. It consists of at least 46 polypeptide chains, plus a tightly bound flavin mononucleotide (FMN) and many iron sulfur centers
Complex I
Complex II is
Succinate Dehydrogenase
Succinate dehydrogenase is reduced by
-from the TCA cycle
FADH2
Embedded in the inner mitochondrial membrane, and is reduced by FADH2
Succinate dehydrogenase
Succinate dehydrogenase then reduces
-makes a branch at the CoQ point in the chain
CoQ
The electrons from FADH2 that to CoQ can also come from glycerol-3-phosphate dehydrogenase as a part of the
G-3-P and fatty acyl CoA dehydrogenase
The acyl CoA dehydrogenase resides in the
Matrix
Accepts 2 electrons from a reduced iron sulfur group of complex I (together with 2 protons) leading to the reduced form
Coenzyme Q (CoQ, ubiquinone)
A small lipid soluble molecule in the membrane; it is the only component that is not a protein, and it can freely diffuse in the inner mitochondrial membrane
CoQ
The reduced form of CoQ, CoQH2 transfers its electrons to
-In complex III
Cytochrome B
Complex III is reduced by CoQH2 and then passes its electrons to
Cytochrome C
Complex III consists of 11 subunits, including
- ) Cytochrome B
- ) Cytochrome C
- ) Fe-S center
Electrons are transferred from CoQ to cyt b to cyt c1, and eventually to the next component
Cytochrome C
Cyt c gets reduced by complex III and it reduces
Complex IV
A single polypeptide chain with a single heme group
Cytochrome C
The only water soluble component of the electron transport chain. It is present in the intermembrane space of the mitochondrial and has a high positive charge on its surface
Cytochrome C
Binds to complex III electrostatically, from the intermembrane space side of the inner mitochondrial membrane and becomes reduced
Cytochrome C
Cyt c is also a trigger for
Apoptosis
The final component of the ETC
Complex IV (cytochrome oxidase)
Complex IV accepts electrons from Cyt c, and then coordinates the transfer of 4 electrons to
Oxygen (reducing it to water)
Consists of 11 polypeptide chains, including cyt a (which contains heme a) and cyt a3 (which contains heme a3), and two copper ions
Complex IV
The heme group of cyt a3 in its reduced state binds
O2
The other cytochromes all have 6 ligands bound to the iron in the heme group and cannot react with
Oxygen
The transfer of 2 electrons from NADH through all the components of the electron transport chain to O2 generates a larger amount of energy (~53kcal/mol) and leads to the formation of
3 ATP molecules
The oxidation of 1 NADH leads to 3 ATP, while oxidation of succinate leads to
2 ATP
Oxidation reduction reactions in the electron transport chain lead to pumping of protons from the matrix to the
Outer side of the inner membrane
There are more protons on the outer side and fewer protons on the matrix side of the inner mitochondrial membrane. This gradient of protons (H+) generates both a
pH gradient and an electrical gradient
Thus the proton gradient generates an electrochemical or chemiosmotic gradient, which provides energy or a force, sometimes called the
Proton motive force
It is this proton-motive force or chemiosmotic gradient which provides the energy to synthesize
ATP
As the components of the electron transport chain are reduced and oxidized, there are 3 sites in electron transport at which a large amount of energy is given off. What are they?
- ) NADH-CoQ reductase (I)
- ) Cytochrome C reductase (III)
- ) Cytochrome C oxidase (IV)
The actual synthesis of ATP takes place in a complex known as
ATP Synthase
Which portion of the ATP synthase is an integral part of the inner mitochondrial membrane?
Fo
Consists of a stalk and globular portion that extend from the inner mitochondrial membrane into the matrix
F1 portion of ATP synthase
The proton gradient that is generated across the inner mitochondrial membrane by the electron transport chain is used to rotate subunits of
Fo