Succinate dehydrogenase oxaloacetate inhibition

Succinate is oxidized to fumarate by succinate dehydrogenase, pro ducing the reduced coenzyme FADH2 (see Figure 9.6). [Note FAD, rather than NAD, is the electron acceptor because the reducing power of succinate is not sufficient to reduce NAD. ] Succinate dehydrogenase is inhibited by oxaloacetate. 

Succinyl CoA is cleaved by succinate thiokinase (also called succinyl CoA synthetase), producing succinate and ATP (or GTP). This is an example of substrate-level phosphory lation. Succinate is oxidized to fumarate by succinate dehydrogenase, producing FADH2. The enzyme is inhibited by oxaloacetate. Fumarate is hydrated to malate by fumarase (fumarate hydratase), and malate is oxidized to oxaloacetate by malate dehy drogenase, producing NADH. 

The fourth control in the cycle is at the conversion of succinate to fumarate via succinate dehydrogenase. This enzyme is inhibited by oxaloacetate, so that if for any reason oxaloacetate accumulates, the enzymes will be inhibited thus, oxaloacetate feeds back and inhibits a reaction that is required for its synthesis. This phenomenon is called negative feedback. (See Chap. 9.)... 

During the terminal stages of electron transfer in complex II, cytochrome bysg is involved however, its specific function is not understood. Oxaloacetate and malonate are competitive inhibitors of succinate dehydrogenase and compete with the substrate for binding at the active site (Chapters 6 and 13). Carboxin and thenoyltrifluoroacetone (Figure 14-7) inhibit electron transfer from FADH2 to CoQ. 

Recent studies suggest that succinate dehydrogenase activity is affected by oxaloacetate. Would you expect the enzyme activity to be enhanced or inhibited by oxaloacetate ... 

Allen et al., 1964), where they are known to catalyze the conversion of oxaloacetate to succinate at a high rate (Krebs and Egglestone, 1941). In propionibacteria, the succinate dehydrogenase is not inhibited by malonate, in contrast with succinate dehydrogenases of the Krebs cycle (Ichikawa, 1955). 

In a broad sense, interconvertible forms of the same enzyme are compartmented in being rendered temporarily inactive by mechanisms such as phosphorylation by a specific kinase, as is the case with pyruvate dehydrogenase (Reed, 1976). Other examples, such as keto-enol tautomerization, can be mentioned as chemical compartmentation. Pogson and Wolfe (1972) have demonstrated that, at pH 7.4, 74% of oxaloacetate is in the keto form, and that a number of enzymes for which oxaloacetate is a substrate bind this form. However, the active species of oxaloacetate responsible for inhibiting succinate dehydrogenase and citrate lyase is the enol form. The balance between the two forms is maintained by a specific tautomerase, and this type of chemical compartmentation must be considered a potentially important factor in regulating metabolic pathways. Since there is little information relating to this point, however, we will not discuss it in detail in this review. 

The Oxaloacetic System (Szent-Gyoi i, 1937).— The wide distribution of the three enzymes, succinic and malic dehydrogenase, and fumarase, si ests that they and their respective substrates participate in many tissue respirations. Addition of malonic acid, which inhibits succinic acid oxidation, leads to an almost complete... 

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