Metabolism Krebs cycle.docx

The tricarboxylic acid cycle (Krebs cycle) Degradation products of carbohydrates, lipids, amino acids are fed into TCA cycle to release energy. TCA cycle has both catabolic and anabolic function= amphibolic. Oxidation= gain of oxygen, loss of H+ and e- Reduction= Loss of oxygen, Gain of H+ and e- NA...

The tricarboxylic acid cycle (Krebs cycle) Degradation products of carbohydrates, lipids, amino acids are fed into TCA cycle to release energy. TCA cycle has both catabolic and anabolic function= amphibolic. Oxidation= gain of oxygen, loss of H+ and e- Reduction= Loss of oxygen, Gain of H+ and e- NAD+ and FAD are key redox co-factors. Link from glycolysis to TCA cycle is Pyruvate dehydrogenase (PDH). Pyruvate must be transported into mitochondrial matrix by pyruvate translocase. CoA links CoA with pyruvate, takes off Co2. Pyruvate is converted into Acetyl CoA. Acetate group is slightly more oxidised therefore the H+ are taken and NAD+ is reduced to NADH+, H+ REDOX reaction called oxidative decarboxylation. The acetate within pyruvate is activated by linking it to coenzyme A which then undergoes further reactions. For each acetyl CoA 2 molecules of Co2 NAD+ and FAD is reduced to NADH and FADH2. 3 NADH and 1 FADH2 1 GTP Acetyl CoA reacts with oxalacetate (citrate synthase) to produce citrate. Citrate is converted to isocitrate (aconitase) and H2O is released. Isocitrate is converted to a-Ketoglutarate (IDH). NAD+ is reduced to NADH and CO2 is produced. a-Ketoglutarate is converted into Succinyl-CoA (a-Ketoglutarate dehydrogenase). Co2 comes off and NADH is produced. CoA activates it. Succinyl-CoA is converted to succinate (succinate thiokinase). GTP is produced and CoA comes off. Succinate is converted to fumarate (succinate dehydrogenase). FADH2 is produced. Fumarate is converted to L-Malate (fumarase). L-Malate is converted finally back oxaloacetate (malate dehydrogenase) and NADH is produced. STEP Enzyme Reaction Type 1 Citrate synthase oxaloacetate + acetyl-CoA citrate condensation 2 Aconitase citrate isocitrate isomerisation 3 Isocitrate dehydrogenase isocitrate α-Ketoglutarate oxidative decarboxylation 4 a-Ketoglutarate dehydrogenase α-Ketoglutarate succinyl-CoA oxidative decarboxylation 5 Succinyl-CoA synthetase succinyl-CoA succinate substrate level phosphorylation 6 Succinate dehydrogenase succinate fumarate oxidation 7 Fumarase fumarate malate hydration 8 Malate dehydrogenase malate oxaloacetate oxidation Carbohydrates can be converted into pyruvate which is then converted to acetyl CoA which enters the cycle. Fatty acids can be converted into acetyl CoA which enters the cycle. Some amino acids can also be converted into acetyl CoA which enters the cycle. Some amino acids is converted to aspartate which is converted to oxaloacetate. Some amino acids can be converted into pyruvate which is then converted into oxaloacetate. FATS CANNOT BE CONVERTED INTO SUGARS Oxidative phosphorylation- the electron transporter chain ETC The inner membrane of the mitochondria is highly impermeable especially to hydrogen ions. The outer membrane is quite permeable. Energy can be stored in ion gradients such as electrochemical gradients is used to establish energy. Electrons from NADH and FADH2 (from TCA cycle) flow through complexes in the inner mitochondrial membrane. These drives export of protons to intermembrane space which produced a proton gradient. Proton motive force is established as protons would like to move back down the gradient into the matrix. The proton gradient is used by ATP synthase to make ATP. Ion gradient is used to produce energy= chemiosmotic theory. The ETC It allows energy from NADH/FADH2 to be obtained in small amounts by series of redox reactions. Starts with NADH which is reduced to NAD+ NADH passes electrons and hydrogens to complex 1. FADH2 is reduced to FAD and passes electrons and hydrogens to complex 2. Both complex 1 and 2 pass the electrons and hydrogen to a cofactor called CoQ. CoQ passes the electrons and hydrogens to complex 3. Complex 3 passes it to another soluble cofactor called cytochrome C. Cytochrome C passes it to complex 4. In complex 4, water is formed as the oxygen is reduced. Electrons flow from reduced to oxidised component. Electrons pass through the ETC by cycles of redox reactions. NADH passes electrons to complex 1. NADH becomes reduced to NAD+. Complex 1 becomes reduced when it receives the electrons. It releases 4H+. Complex 1 passes the electrons to CoQ. It becomes reduced when it accepts the electrons and hydrogens. CoQ passes electrons to complex 3 and it becomes reduced when it accepts the electrons and hydrogens. 4 H+ are pumped out. Complex 3 passes electrons to cytochrome C. The oxidised forms of cytochrome C accepts the electrons to become reduced. Cytochrome C only accepts electrons. Cytochrome C passes electrons to complex 4 which then becomes reduced after accepting them. Releases 2H+ The electrons are passed onto oxygen to produce water. The process is same for FADH2 except the facts that FADH2 passes hydrogens and electrons to complex 2 not complex 1 and fewer H+ pumped out. Therefore, less energy from FADH2 compared to NADH.