Citric acid cycle part 2 + Glyoxylate Cycle

• Entry to the citric acid cycle and metabolism through it are controlled
• Citric acid cycle is amphibolic as it provides energy and metabolites that are not wasted
• Pyruvate dehydrogenase complex is an irreversible reaction between glycolysis and TCA cycle, where acetyl CoA cannot be converted back to pyruvate
• The need for energy regulates the citric acid cycle capacity at the pyruvate dehydrogenase step and at the three rate controlling steps of the citric acid cycle that are highly exergonic
• Regulatory mechanisms that can inhibit or activate depend on substrate availability, product inhibition, covalent modification, and allosteric effects
• Product inhibition is that If the product of the reaction is high, it would inhibit the enzyme
• Allosteric effects changes the conformation of the enzyme
• Covalent modification is usually through phosphorylation
• Electrons are funnelled into ATP synthesis by the electron transport chain, then oxidative phosphorylation
• When NADH undergoes ETC then Oxidative phosphorylation, complete oxidation would generate 2.5 ATP. Since there are 3 NADH per molecule of Acetyl CoA, it yields 7.5 ATP
• When FADH2 undergoes ETC then oxidative phosphorylation, complete oxidation would generate 1.5 ATP. Since there is 1 FADH2 per molecule of Acetyl CoA, it yield 1.5 ATP
• GTP and ATP can be interconverted by nucleoside diphosphate kinase per molecule of Acetyl CoA, in which if it undergoes straight to oxidative phosphorylation, it produces 1 ATP
• In 1 Acetyl CoA, The overall number of ATP produced with NADH, FADH2, and GTP/ATP is 10 ATP
• 2 NADH from glycolysis is produced from from 2 Glyceraldehyde 3 phosphate that enters in Glyceraldehyde 3 phosphate dehydrogenase forming 5 ATP
• 2 ATP is made in Glycolysis through the reaction of Phosphoenolpyruvate and pyruvate kinase with ADP as its co factor
• In the conversion of 2 Pyruvate to 2 Acetyl CoA by the pyruvate dehydrogenase complex, 2 molecules of NADH are produced which yields 5 ATP
• 2 Acetyl CoA would enter the citric acid cycle to generate 6 NADH, 2 FADH2, and 2 GTP forming 20 ATP
• The overall number of ATP produced from Glycolysis to Oxidative phosphorylation is 32
• Aerobic metabolism of the pyruvate has more ATP than anaerobic metabolism of 2 ATP, but it is more processed
• Acetyl CoA can be used aerobically to CO2 or a raw material that is reversible for lipids
• Lipids can be beta oxidized to acetyl CoA
• Pyruvate dehydrogenase complex is regulated by product inhibition and covalent modification
• In the pyruvate dehydrogenase complex, Acetyl CoA inhibits the second enzyme transacetylase
• In the pyruvate dehydrogenase complex, NADH inhibits the third enzyme dihydrolipoyl dehydrogenase
• High amounts of NADH and acetyl CoA inform the enzyme that the energy needs of the cell have been met or fatty acids are being degraded to produce Acetyl CoA and NADH
• In the covalent modification of eukaryotic pyruvate dehydrogenase, E1 is inactivated by the specific phosphorylation of one of its Serine residues catalyzed by pyruvate dehydrogenase kinase
• In the covalent modification of eukaryotic pyruvate dehydrogenase, E1 is reactivated when the phosphoryl group is hydrolyzed through pyruvate dehydrogenase phosphatase
• When the blood glucose is high, it releases insulin in the pancreas. Activating the kinase and glycogen synthesis, and deactivating the PDH complex
• Excess glucose is funneled to storage mechanism as glycogen
• The ATP/ADP indicates the level of charge
• If ratio of ATP/ADP is high, it would have high energy charge because the tissue does not need to consume ATP and is bound for resting
• At rest, the NADH/NAD+, acetyl CoA/CoA and ATP/ADP ratios are high which promotes phosphorylation and deactivation
• When exercise begins, ADP and pyruvate increases, ATP is consume, and glucose is converted to pyruvate
• At work, ADP and pyruvate activates PDH by deactivating the kinase, and phosphatase is stimulated by Ca2+ when it is released by exercise
• The three enzymes that are likely to function far from equilibrium and are the control points are citrate synthase, NAD+ dependent isocitrate dehydrogenase, and alpha Ketoglutarate dehydrogenase
• These control points are regulated primarily by the concentration of ATP and NADH which are the main products of citric acid cycle
• In citrate synthase enzyme, the oxaloacetate in reaction with Acetyl CoA must be proceeded, or otherwise oxaloacetate would stock up
• The main control points include isocitrate dehydrogenase and alpha ketoglutarate dehydrogenase
• Excess citrate would inhibit isocitrate dehydrogenase and would be transported to the cytosol to inhibit PFK for glycolysis to stop
• Isocitrate dehydrogenase are stimulated by ADP and NAD+; ATP and NADH are inhibitory; and ADP and NAD+ are abundant only when the energy charge is low