Located in the mitochondrion, the TCA cycle is closely associated with the pyruvate dehydrogenase complex, the electron transport system and other pathways, all of which function as a highly coordinated unit. The TCA cycle is the central, common pathway by which fuels are oxidized, and it also participates in major biosynthetic pathways. In its oxidative role, its major products are, GTP and the reduced coenzymes NADH and FADH2, which furnish large amounts of free energy for the synthesis of ATP by oxidative phosphorylation. In its biosynthetic role, it provides essential intermediates for the synthesis of glucose , fatty acids, amino acids and heme, as well as the ATP required for their biosynthesis. The activity of the TCA cycle is tightly regulated by substrate supply, by allosteric effectors and control of gene expression so that fuel consumption is coordinated with energy production.
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- In beri-beri, the vitamin thiamine is deficient. Which intermediates would accumulate, and explain why.
- Based on rates of oxygen consumption, which tissues would be the most critically impaired because of genetically defective enzymes of the TCA cycle?
- Compare the regulation of the pyruvate dehydrogenase complex to the regulation of cytosolic enzymes by phosphorylation/dephosphorylation reactions.
- Predict the consequences of deficiencies in TCA cycle enzymes such as succinate dehydrogenase, fumarase or malate dehydrogenase.
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