Oxidative phosphorylation

• Oxidative phosphorylation is the process that conserves the energy from ETC by phosphorylation of ADP to ATP
• The energy read from the oxidation of NADH is enough to phosphorylate the formation of ATP
• The chemiosmotic theory explains how a proton gradient links electron transport to ATP synthesis. Where the concentration of proton in the intermembrane space becomes more higher and more negative in matrix than before producing a negative membrane potential or proton motive force
• ATP would be synthesized by ATPase if the proton flown from the intermembrane space proceeds to the matrix when proton motive force was initiated
• In Peter Mitchell's chemiosmotic hypothesis, the free energy of electrons flown are conserved by pumping H+ from the mtochondrial matrix to the intermembrane space to create an proton gradient across the inner mitochondral space. It would harness ATP production
• The structure of ATP synthase looks like a ball (F1) and stick (F0)
• F1 subunit sticks to the matrix, which contains the ATPase activity which has an Alpha, Beta, Gamma, Epsilon, and Delta
• The alpha and beta subunits are arranged alternately forming a hexamer resulting to a3b3, and both binds in nucleotides but beta subjects to ATP synthesis
• The hexamer F1 is connected to the C ring/F0 by the central stalk gamma and epsilon and an exterior column b2, delta, and a subunits
• ATP Synthase is composed of a proton conducting unit and a catalytic unit
• There are 3 conformations of the beta subunit depending on the phase of the gamma subunit that interacts with it
• The a column connected to the c ring has a white structure named proton channels, where protons enter there in either by the intermembrane space or matrix
• The c ring is made of a polypeptide chain that forms aa helices, and aspartic acid is in the middle which can be protonated or deprotonated. It has 10 to 18 c subunits depending on the cell
• If aspartic acid becomes aspartate, the charge becomes negative, and it does not assist the bilayer
• The c ring rotates but the aspartate when removed its proton due to its hydrophilic nature. It stabilizes the movement due to the thermodynamics of the hydrophobic nature of the bilayer
• When the intermembrane space has high amounts of protons, while the matrix has lesser protons, the protons above would flow through it and the c ring becomes protonated. Which results for the c ring to rotate until released proton to the matrix for ATP synthesis
• The hexamer does not rotate, and the c subunits and gamma subunits rotate causing it to change the conformation of the beta subunit
• The F0 subunit is a hydrophobic segment that contains the proton channel of the complex
• Proton flow through ATP synthase leads to the release of tightly bound ATP
• When ADP is phosphorylated with Pi and H+, it forms a pentavalent intermediate which is then hydrolyze to form ATP and H2O
• The role of proton gradient releases the ATP from the synthase and not forming ATP
• The beta subunit is performed in ATP synthesis is differentiated in accordance to its interaction to the gamma subunit, such as T, O, or L
• T is tight with ATP and it cannot be released
• O can bind with ADP and Pi
• The beta subunit connects to the central stalk gamma subunit and epsilon
• L can release ATP
• The gamma subunit can be rotated counterclockwise, which interconverts the three beta subunits
• The subunit in T form interconverts ADP and Pi and ATP but does not allow ATP to be released. When T is rotted 120 CCW, T is converted to O allowing ATP to be released. ADP and Pi binds with O form. Another 120 degrees rotation allow substrates to be trapped in L form
• When the proton flows through the a subunit, the aspartate in the c ring becomes protonated and can rotate c ring and release ATP from the beta subunit
• The a subunit include two half channel such as cytoplasmic half channel and matrix half channel that allow protons to enter and pass partway in contact with c ring but not completely through the membrane
• The complete oxidation of glucose yields about 30 molecules of ATP because the NADH produced in the cytosol is transported by the glycerol 3 phosphate shuttle.
• Agents that dissipate the proton gradients uncouple electron transport and ATP synthesis
• 2,4 Dinitrophenol in the cytosol has a low pH that can be diffused in the inner mitochondrial membrane and at high pH. Its energy is released as heat which deprotonates the DNP
• Adipose tissue activates the uncoupling protein (UCP-1) releases heat during cold conditions which permits the influx of protons in the mitochondria without the synthesis of ATP
• The control of oxidative phosphorylation relates to the glycolysis, citric acid cycle and pyruvate dehydrogenase complex
• The energy charge regulates the use of fuels. The synthesis of ATP from ADP and Pi controls the flow of electrons from NADH and FADH2 to oxygen. The availability of NAD+ and FAD in turn control the rate of TCA
• Although aerobic metabolism such as cytochrome c oxidase is efficient, it still lead to the production of reactive oxygen species
• Uncontrolled oxidative stress/radicals can lead to various diseases
• All living processes take place within a redox environment
• The redox state is regulated within a narrow range because of redox sensitive nature of many pathways