Dehydrogenation of succinate

The biological dehydrogenation of succinic acid described in Section 5 8 is 100% stereoselective Only fumaric acid which has a trans double bond is formed High levels of stereoselectivity are characteristic of enzyme catalyzed reactions... 

Oxidation may take place by a modified tricarboxylic acid cycle in which the production of CO2 is coupled to the synthesis of NADPH and reduced ferredoxin, and the dehydrogenation of succinate to fumarate is coupled to the synthesis of reduced menaquinone. This pathway is used, for example, by Desulfuromonas acetoxidans and in modified form by... 

Although enzymes catalyze only certain reactions or certain types of reaction, they are still subject to interference. When the activated complex is formed, the substrate is adsorbed at an active site on the enzyme. Other substances of similar size and shape may be adsorbed at the active site. Although adsorbed, they will not undergo any transformation. However, they do compete with the substrate for the active sites and slow down the rate of the catalyzed reaction. This is called competitive inhibition. For example, the enzyme succinic dehydrogenase will specifically catalyze the dehydrogenation of succinic acid to form fumaric acid. But other compounds similar to succinic acid will competitively inhibit the reaction. Examples are other diprotic acids such as malonic and oxalic acids. Competitive inhibition can be reduced by increasing the concentration of the substrate relative to that of the interferent so that the majority of enzyme molecules combine with the substrate. 

The enzyme is unable to bind both S and I at the same time and in competitive inhibition, the enzyme-inhibitor complex El does not react with substrate S. Competitive inhibitors often resemble substrate structurally. As an example we can mention malonate, which is an inhibitor for dehydrogenation of succinate of a enzyme succinic dehydrogenase and resembles the structure of succinate (Figure 6.35)... 

Reactions analogous to those of the TCA-cycle are found in the biosynthesis of leucine and lysine (Fig. 4). Similarly, the sequence of reactions represented by the dehydrogenation of succinate by a fla-voenzyme, followed by hydration of fumarate to ma-late, then dehydrogenation of malate by a NAD-linked dehydrogenase, finds a counterpart in the initial stages of fatty acid degradation (see). 

Dehydrogenation of succinic acid into fumaric acid is catalyzed by succinate dehydrogenase, a mitochondrial FAD-enzyme (Singer and Kearney, 1963). 

Collaboration of the NAD system in the dehydrogenation of succinate is thermodynamically impossible because the nicotinamide system with a redox potential of En = —0.32 volt is too weak an oxidizing agent. The flavoprotein (Et, = —0.06), in contrast, can attain equilibrium with the system succinate/fumarate (E = 0.00). It is almost a general rule that the introduction of a C—C double bond into a saturated chain requires flavojrroteins. 

Dehydrogenation of succinate introduces a C—C double bond to give rise to the frans-compound fumarate (step 7). The enzyme succinate dehydrogenase is a flavoprotein and is a member of the respiratory chain (cf. Chapt. X-4). This reaction is inhibited by malonate—the classical example of competitive inhibition The wrong substrate is attached to the enzyme, but cannot undergo the reaction for simple chemical reasons. 

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