TRICARBOXYLIC ACID CYCLE TCA CYCLE DEHYDROGENATION OF SUCCINATE TO FUMARATE

12.5.      Dehydrogenation of succinate to fumarate

The oxidation of succinate to fumarate is the only dehydrogenation reaction in the citric acid cycle in which NAD⁺ does not participate. In this reaction the hydrogen is directly transferred from the succinate to flavoprotein enzyme and fumarate is formed. The succinate dehydrogenase is a flavoprotein located on the inner mitochondrial membrane. The enzyme contains the reducible prosthetic group flavin adenine dinucleotide (FAD) as the coenzyme. FAD functions as the hydrogen acceptor in this reaction, rather than NAD⁺. this is because the free energy change is insufficient to reduce NAD⁺.

In succinate dehydrogenase, the isoalloxazine ring of FAD is covalently linked to a histidine side chain of the enzyme.  This is a reversible reaction.

Fumarate is hydrated to form L-malate in the presence of fumarate hydratase (formerly known as fumarase). This is a reversible reaction and involves hydration in malate formation and dehydration in fumarate formation.

Fumarate hydratase is highly specific and catalyzes trans addition and removal of H and OH and  does not act on malate, the cis-isomer of fumarate.

Malate dehydrogenase is a good example of a reaction that has a net flow opposite to an unfavorable equilibrium. That is the oxidation of malate by NAD⁺ to produce oxaloacetate + NADH + H+ has a ΔG°' of + 7 kcal/mole.