number 8 Done by Ali Yaghi Corrected by Mamoon Mohamad Alqtamin Doctor Nafeth Abu Tarboush 0 P a g e
Oxidative phosphorylation Oxidative phosphorylation has 3 major aspects: 1. It involves flow of electrons from NADH and FADH2 in TCA cycle through a chain of membrane bound carriers (prosthetic groups), and keep transporting them from one complex to another until they reach oxygen; the final electron acceptor. Note: Because there is a difference in potential, there must be a difference in energy (ΔG= -nfδe). 2. Energy produced from the movement of electrons in the electron transport chain is used to pump protons from the matrix of the mitochondria to theintermembraneous space through pumps in the inner mitochondrial membrane. Note: The free energy available is exergonic Note: The inner mitochondrial membrane is proton-impermeable membrane 3. The transmembrane flow of protons down their electrochemical gradient provides the free energy for synthesis of ATP (energy is used to couple inorganic phosphate with ADP to produce ATP). Note: Oxophoswas discovered by Peter mitchelin 1961(chemiosmotic theory). 1 P a g e
How does the electron transport chain generate ATP from NADH? NADH can move freely through the solution (martix). Enzymes that are used to produce NADH are: a. Isocitrate dehydrogenase complex b. Alfa-ketoglutarate dehydrogenase complex c. Malate dehydrogenase. NADH moves to its receptor in ETC which is called complex 1. It is the point of transmitting electrons from NADH. Complex 1 takes electrons from NADH as H- (hydride ion). Note that Complex 1 is a dehydrogenase (NADH dehydrogenase); because it contains FMN which acts as an acceptor for electrons from NADH and transfer them to the iron-sulfur clusters. The first thing that takes electrons from NADH is FMN and it turns into FMNH2. Now complex 1 is reduced: NADH (2e), FMNH2 (2e), IRON-SULFER clusters (2e), CoQ. Note: Iron-sulfur clusters are present in complex 1. Note: Fe can transport 1 electron at a time, and can transport 2 electrons in two stages. How does the electron transport chain generate ATP from FADH2? FADH2 can't move freely in the matrix because it is always bound to a protein which is succinate dehydrogenase in ETC. Succinate dehydrogenase is the only intact between citric acid cycle and electron transport chain, and it is suspended in the matrix surface of the inner membrane. So, Succinate dehydrogenaseis complex 2. It has FAD and iron-sulfer clusters so it works as dehydrogenase. Complex 1 gives its electrons to complex 3, so does complex2 through the CoQ (Complex 1 and 2 do not have any connection). 2 P a g e
How do electrons move from complex 1 and 2 to complex 3? Electrons move through a lipid soluble electron carrier that has a hydrophilic part that attaches to electrons. This material is called coenzyme q or ubiquinone. The carrier must be lipid soluble; because if a hydrophilic carrier is used, it can't transport complex 2 electrons to complex 3, because complex 2 isn't spanning the membrane. Ubiquinone Ubiquinone is a cyclic di-ene structure + long hydrocarbon chain. Carries electrons through the IMM. Can accept either 1 electron or 2 electrons, because it has 2 carbonyl groups. Act at the junction between a 2-electron donor and 1-electron acceptor. Note: Co-Q is prescribed to patients who suffer from myocardial infarction (dead heart tissue), because it increases the amount of ATP produced per time; compensating dead tissue. Note: Toxic materials that attack complex 3 cause death. The damage from toxins that attack complex 1 or 2 aren't as bad as complex 3. Complex 3 Complex 3 is called cytochrome bc1. Cytochrome means that the protein works as an electron transporter and has a heme group. This complex has different types of heme (heme b and c), and has iron sulfer clusters. These features make it work as an oxidoreductase; reduction by getting electrons from CoQ and oxidation by giving electrons to cytochrome C. 3 P a g e
How do electrons move from complex 3 to complex 4? Since these complexes are spanning the membrane, the carrier is outside the membrane. The carrier is a protein called cytochrome c, which has the capacity of transporting 1 electron per time. Complex 4 is called Cytochrome C oxidase because it oxidizes Cytochrome C; by taking the transported electron. وال ( hemoglobin. Complex 4 has higher affinity toward O2 than myoglobin and (كيف بدو يدخل الخلية Complex 4 It is an oxidoreductase since it turns O2 into water, and it works as an oxidoreductase because it has 2 copper atoms and 2 heme groups. The movement of electrons: As electron as is, like in the heme. Hydrogen atoms: FADH2. Hydride ions: NAD to NADH. Requirements of OxPhos: 1. Redox reaction: electron donor (NADH or FADH2) & electron acceptor (O2) 2. Impermeable inner mitochondrial membrane 3. Proteins of the electron transport chain 4. ATP synthase 5. Potential difference between donor and acceptor ATP synthase: complex 5 It has 2 parts: F0 in the membrane, and F1 in the matrix (where ATP is synthesized) 4 P a g e
F0 portion: It is cylindrical in shape It can rotate within the membrane It is connected to an alpha subunit It is composed from 12 C subunits and an alpha subunit. Alpha subunit is where the H+ ions pass through. It isn't a continuous channel, it is separated. F1 portion: 3 alpha subunits and 3 beta subunits arranged alternatively. Alfa subunits are structural. Beta are catalytic subunits. Angled Gama subunits are produced from C subunits. Mechanism of working: The proton passes in the channel, faces a C subunit (which has deprotonated glutamic acid), then H+ attaches to this subunit and glutamic acid becomes protonated, then it rotates exposing another c subunit, and so on. This process continues until protonated glutamate reaches the other opening of the channel. ph and pka at the other opening make glutamate deprotonated, and shut the H+ ion toward the matrix.the reason for doing this is to make rotation in C subunits. While the C subunits are rotating in the membrane, the angled gama subunit hits different beta subunits with each rotation. When a subunit hits another subunit, a conformational change happens. And there are 3 conformational changes: open, loose and tight. At first it is loose. Loose has high affinity for ADP with in-organic phosphate, when a conformational change is happening, it is turned into tight: which makes ADP and Pi close together and generate ATP. Then another change takes place that makes the subunit loose, which has low affinity for ATP, so ATP is released. Note: ATP synthase can move in reverse, also (make ADP +Pi from ATP). 5 P a g e