Succinate Oxidation ,Fumarate Hydration and Malate Oxidation in TCA

Succinate is oxidized to fumarate by succinate dehydrogenase, as its coenzyme FAD is reduced to FADH2 (see Fig. 1). Succinate dehydrogenase is the only enzyme of the TCA cycle that is embedded in the inner mitochondrial membrane. As such, it functions as Complex II of the ETC . [Note: FAD, rather than NAD+, is the electron acceptor because the reducing power of succinate is not sufficient to reduce NAD+.]

 Fumarate hydration
Fumarate is hydrated to malate in a freely reversible reaction catalyzed by fumarase (fumarate hydratase, see Fig. 1). [Note: Fumarate is also produced by the urea cycle , in purine synthesis , and during catabolism of the amino acids phenylalanine and tyrosine .]

Figure 1:  Formation of malate from α-ketoglutarate. FAD(H2) and NAD(H) =flavin and nicotinamide adenine dinucleotides; GDP and GTP = guanosine diand triphosphates; ~ = high-energy bond; CoA = coenzyme A.
 Malate oxidation
Malate is oxidized to OAA by malate dehydrogenase (Fig. 2). This reaction produces the third and final NADH of the cycle. The ΔG⁰ of the reaction is positive, but the reaction is driven in the direction of OAA by the highly exergonic citrate synthase reaction. [Note: OAA is also produced by the transamination of the amino acid aspartic acid .]

Figure 2:  Formation (regeneration) of oxaloacetate from malate. NAD(H) = nicotinamide adenine dinucleotide.

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