Oxidative phosphorlyation.docx

ATP synthase is located in the inner mitochondrial membrane. Also called F1F0-ATPase It uses and makes H+ gradient to synthesise ATP. It has a ‘Knob and stalk’ structure. F1 contains the catalytic subunits and sticks out of the mitochondrial matrix. F0 has a proton channel and remains embedded in th...

ATP synthase is located in the inner mitochondrial membrane. Also called F1F0-ATPase It uses and makes H+ gradient to synthesise ATP. It has a ‘Knob and stalk’ structure. F1 contains the catalytic subunits and sticks out of the mitochondrial matrix. F0 has a proton channel and remains embedded in the mitochondrial membrane. Molecular structure of F1F0-ATPase. ATP-synthase rotational motor overview The H+ gradient driver H+ passage through F0. This causes c-ring to rotate in the membrane. Drives rotation of the gamma spindle that connects F0 to F1. Causes confirmational change in the alpha beta hexamer that results in ADP and Pi converted to ATP and water. The alpha beta hexamer doesn’t turn, it stays in place by b and gamma subunits. How does the C ring rotate? When H+ enters from the a-half channel, it binds to COO-. It protonates the carboxylic acid. Once its protonated, it’s no longer stable for it to stay next to a negative charged COO- so it causes it to rotate away until the H+ leaves from the other half of the a-half channel. How the c-ring turning converts ADP to ATP. Clockwise rotation of gamma subunit causes confirmational change of the 3 beta subunits. There are 3 confirmational states: First form is open, and nothing binds well (the substrates and the products come off easily) Second form is called loose, ATP and Pi from mitochondrial matrix bind to the active site of the beta subunit. The third form called tight, gamma subunit binds to ADP and Pi very tightly and converts them into ATP. ATP cannot be released so it has to go back to open stage to allow it to be released. The alpha/beta hexamer doesn’t turn but the gamma spindle turns via the energy from the proton gradient. It goes from open to lose to tight and cycle repeats. 3 protons are required for each confirmational change. Aerobic glucose utilization 2 ATP from glycolysis 2 NADH from glycolysis 2 NADH from pyruvate dehydrogenase 6 NADH from TCA cycle (1 glucose produces 2 pyruvates hence reaction runs twice.) 2 FADH2 from TCA cycle (1 glucose produces 2 pyruvates hence reaction runs twice.) 2 GTP from TCA cycle (1 glucose produces 2 pyruvates hence reaction runs twice.) Total= 30 ATP So more ATP is produced from oxidative phosphorylation than glycolysis. But…. Some ATP is used for the process such as transportation of NADH from cytosol into mitochondrial matrix) The production of NADH from electron transport chain and the phosphorylation in the ATP synthase are tightly controlled and linked. If proton motive force has built up, ATP can be synthesised, if not then it cannot be synthesised. There are important sites of control in complex 4 (cytochrome C oxidase) and adenine nucleotide translocase which swaps ADP and ATP from one side of membrane to another.