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The three reactions in the citric acid cycle (TCA) that produce NADH are:
1. Isocitrate to α-ketoglutarate: This step is catalyzed by isocitrate dehydrogenase and involves the oxidation of isocitrate and the reduction of NAD+ to NADH.
2. α-ketoglutarate to succinyl CoA: This reaction is catalyzed by α-ketoglutarate dehydrogenase complex and involves the oxidative decarboxylation of α-ketoglutarate, producing CO2 and NADH.
3. Malate to oxaloacetate: This step is catalyzed by malate dehydrogenase, where malate is oxidized to oxaloacetate, and NAD+ is reduced to NADH.
While these reactions don't directly involve molecular oxygen, they are strongly inhibited under anaerobic conditions because NADH is a crucial electron carrier in the electron transport chain (ETC). The ETC, which is located in the mitochondria, uses the electrons from NADH to drive the production of ATP through oxidative phosphorylation. Under anaerobic conditions, the ETC is shut down, leading to a buildup of NADH. This buildup inhibits the TCA cycle reactions that produce NADH because the enzymes involved require NAD+ as a cofactor. Without the removal of NADH, the TCA cycle cannot proceed efficiently.