The tricarboxylic acid cycle is a series of metabolic reactions, involving both catabolism and anabolism in its cycle, to metabolise glucose or fatty acids or amino acids. Aerobic glycolysis leads to the TCA cycle producing two pyruvate, which are to be used as an Acetyl COA supply. The main functions of the TCA cycle are to improve ability of respiration to produce energy in the form of NADH carrier co enzymes which pump electrons into the electron transport chain which then makes ATP using the motility involving ATP synthetase. One NADH leads to 2.5 ATP molecules being formed. Another function is to produce metabolic precursurs for biosynthesis.
The TCA cycle is initiated when an irreversible condensation reaction involving acetyl COA – SH binding to oxoaloacetate, which is catalysed by citrate synythetase producing the 6 carbon molecule Citrate. Citrate once formed then undergoes an isomerisation reaction in the presence of aconitase, turning first the citrate into an intermediate known as cis-aconitase and then into isocitrate. The 6 carbon Isocitrate is then irreversibly catabolised via an oxidative decarboxylation by the enzyme Isocitrate dehydrogenase which is like PDH as it is a multi enzyme complex. The intermediate oxal succinate is formed which is quickly converted to the 5 carbon Alpha ketoglutarate, releasing a CO2 molecule and a reduced NAD for the electron transport chain. Another oxidative carboxylation occurs due to the enzyme alpha ketoglutaraten and the Coenzyme COA-SH, this time turning alpha keto glutarate into four carbon Succinyl COA causing a CO2 and a reduced NAD to be released. Succinate synthase then causes the release of GTP a denominator of ATP which is readily converted in to the ATP during the only example of substrate level phosphorylation. Succinate is formed, in the next reaction the Succinate undergoes an oxidation reaction in the presence of succinate dehydrogenase causing the Co enzyme FAD to become reduced to FADH2 forming fumarate. Fumarate then undergoes a hydration reaction in the presence of fumarase to form malate. Malate is then the last step before replenisihing the oxoaloacetate, malate dehydrogenase causes the oxidation of the malate forming the last NADH and producing Oxoaloacetate.
Regulation of the TCA cycle is important so that products do not becois me overproduced and reactants are not overused. The regulation involves the inhibition of four important enzymes of the TCA cycle. By inhibiting the enzymes you can control how much product is produced by that enzyme.
The first enzyme that is regulated is the Pyruvate Dehydrogenase complex, this is an enzyme that shows allosteric properties, which means it is inhibited by its product and stimulated by its reactants. The enzyme is inhibited by high acetyl COA concentration, It is inhibited by high amounts of reduced NAD and High GTP.
The second enzyme is the citrate synthetase molecule this is stimulated by high acetyl choline but inhibited by high atp, nadh and alpha ketoglutarate.when there is plenty of atp tca is slowed and acetyl coa stored as fats.isocitrate dehydrogenase is inhibited by high atp and nadh2, alpha keto glutarate inhibited by succinyl coa and nadh2.