Isocitrate dehydrogenase reaction
NAD oxidizes the alcohol on isocitrate to form a ketone. Then the carboxyl group is a the beta position and can leave as CO2 to form alpha-ketoglutarate.
Oxidation by alpha-ketoglutarate dehydrogenase
What are the reversible steps in the overall citric acid cycle?
Oxaloacetate -> Citrate, Isocitrate -> alpha-ketoglutarate, alpha-ketoglutarate -> succinyl CoA
What TCA reaction is unfavorable but pushed forward because of the overall energy of the reaction?
Malate -> Oxaloacetate
What are the two major factors that regulate the TCA cycle?
NAD/NADH ratio and ADP. When NAD levels are high, it means your are expending fuel and NADH is being used to make more ATP in the ETC. NAD is also used to catalyze TCA reactions and fuel is burned. If there is no ADP around, it means you are using very little energy and fuel will not be burned in the TCA cycle.
Where does ADP act to promote fuel burning in the TCA cycle?
Allosteric regulation of isocitrate dehydrogenase.
You've just eaten and are resting. Pyruvate is being oxidized to lots of Acetyl CoA. Where does your food go from there?
It can be converted to oxaloacetate via the pyruvate carboxylase complex. Oxaloacetate is then converted to citrate where it builds up because you are resting and ADP levels are low and NADH levels are high. The citrate is taken out to the cytoplasm to be stored as fat.
What role does pyruvate carboxylase play when you decide to start exercising?
Acetyl CoA enters from fatty acid oxidation and stimulates pyruvate carboxylase to for oxaloacetate. Formation of oxaloacetate fills up the TCA and you are ready to proceed with oxidation to generate more energy.
What pathways are reliant on pyruvate carboxylase activity?
TCA cycle and fatty acid biosynthesis both need citrate. Gluconeogenesis needs phophoenolpyruvate. Aspartate is also needed by the brain, liver and bone marrow.