Citric acid cycle, reactions fumarate hydration

Addition of water to a double bond is a reaction that we find in several biochemical pathways. For instance, the citric acid cycle is a key metabolic pathway for the complete oxidation of the sugar glucose and the release of the majority of the energy used by the body. It is also the source of starting materials for the s)m-thesis of the biological molecules needed for life. The next-to-last reaction in the citric acid cycle is the hydration of a molecule of fumarate to produce a molecule called malate. 

Acid-catalyzed hydration of isolated double bonds is also uncommon in biological pathways. More frequently, biological hydrations require that the double bond be adjacent to a carbonyl group for reaction to proceed. Fumarate, for instance, is hydrated to give malate as one step in the citric acid cycle of food metabolism. Note that the requirement for an adjacent carbonyl group in the addition of water is the same as that we saw in Section 7.1 for the elimination of water. We ll see the reason for the requirement in Section 19.13, but might note for now that the reaction is not an electrophilic addition but instead occurs... 

Steps 7-8 of Figure 29.12 Hydration and Oxidation The final two steps in the citric acid cycle are the conjugate nucleophilic addition of water to fumarate to yield (S)-malate (L-malate) and the oxidation of (S)-malate by NAD+ to give oxaloacetate. The addition is cataiyzed by fumarase and is mechanistically similar to the addition of water to ris-aconitate in step 2. The reaction occurs through an enolate-ion intermediate, which is protonated on the side opposite the OH, leading to a net anti addition. 

The conversion of fumaric acid to malic acid is an important biological hydration reaction. It is one of a cycle of reactions (Krebs citric acid cycle) involved in the metabolic combustion of fuels (amino acids and carbohydrates) to C02 and H20 in a living cell. 

Pyrophosphate is rapidly hydrolyzed, and so the equivalent of four molecules of ATP are consumed in these reactions to synthesize one molecule of urea. The synthesis of fumarate by the urea cycle is important because it links the urea cycle and the citric acid cycle (Figure 23.17). Fumarate is hydrated to malate, which is in turn oxidized to oxaloacetate. Oxaloacetate has several possible fates (1) transamination to aspartate, (2) conversion into glucose by the gluconeogenic pathway, (3) condensation with acetyl CoA to form citrate, or (4) conversion into pyruvate. 

The electrophiJic addition of water to a molecule containing a double bond, known as hydration, is a reaction that is important biologically. One example is the hydration of fumarate to form malate, one of the steps in the citric acid cycle (also known as the Krebs cycle). 

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