Succinic acid dehydrogenase

Fig. 3. Krebs citric acid cycle. Enzymes involved (1) Condensing enzyme (2) aconitase (3) isocitric acid (4) a-ketoglucaric acid dehydrogenase (4) a succinic acid thiokinasc (5) succinic acid dehydrogenase (6) fumarasc (7) malaic acid dehydrogenase. Abbreviations CA = citric acid ACOM = eij-aconitic acid KG = a-ketoglutaric acid SIC = succinic acid FA = fumaric acid MA = malic acid OA = oxalaceiic acid...

Wood and coworkers have demonstrated that pigeon liver mince poisoned with malonate is unable to convert C 02 into isotopic succinate but can direct the isotope into malate and fumarate as well as into the a-carboxyl of a-ketoglutarate (see Fig. 5). On the other hand, non-poisoned liver possesses the ability to anaerobically fix C 02 in succinic acid as well as fumaric and malic acids. The dicarboxylic acids invariably contain the isotopic carbon predominantly in their respective carboxyl groups. These important experiments provide conclusive proof for two main concepts. First, that malonate specifically inhibits succinic acid dehydrogenase and hence blocks completely the formation of succinic from fumaric acid. Secondly, there must be two routes by which succinate is formed. By the first pathway, pyruvate can condense with... 

The microbiostatic action of benzoic acid is based on different inhibition mechanisms, mainly many enzymes in the microbial cell are inhibited (Bosund, 1962 Menon et al., 1990). E.g. in yeast, enzymes that control the acetic acid metabolism and oxidative phosphorylation are inhibited. Benzoic acid appears to intervene at various points in the citric acid cycle, especially that of a-ketoglutaric acid and succinic acid dehydrogenase. Besides its enzyme-inactivating effects, benzoic acid also acts on the cell wall. The types of action of benzoic acid are sometimes very similar to those of sorbic acid, although many more data exist for the latter. 

Benzoic acid activity is directed both to cell walls and to inhibition of citrate cycle enzymes (a-ketoglutaric acid dehydrogenase, succinic acid dehydrogenase) and of enz)mies involved in oxidative phosphorylation. 

Disorders of GABA Vitamin B6-dependent seizures Often an absence of succinic semialdehyde dehydrogenase Hypotonia, ataxia, mental retardation in older child. Increased urine 4-OH-butyric acid. Pyridoxine (B6-dependent disorder) Inhibitors of GABA transaminase... 

Succinic semialdehyde dehydrogenase deficiency. Patients have mental retardation, cerebellar disease, and hypotonia. They excrete large amounts of both succinic semialdehyde and 4-hydroxybutyric acid. There is no known therapy. 

Gupta M, Polinsky M, Senephansiri H, Snead OC, Jansen EEW, Jakobs C, Gibson KM (2004) Seizure evolution and amino acid imbalances in murine succinate semialdehyde dehydrogenase (SSADH) deficiency. Neurobiol Dis 16 556-562... 

A procedure for determining the absolute configuration of the tritiated succinic acid had already been developed, which involved partial oxidation on succinate dehydrogenase [45]. Applying this method it was then possible to show that the tritiated succinic acid of interest had the (S) configuration, and this in turn established the (5S) configuration of the tritiated /3-lysine from which it had been derived. Inspection of Fig. 28 reveals that the /3-lysine mutase reaction takes place with inversion at the C-5 of the substrate. 

Figure 6.3. GABA shunt as an alternative to a-ketoglutarate dehydrogenase in the citric acid cycle. 2-Oxoglutarate dehydrogenase, EC 1.2.4.2 glutamate decarboxylase, EC 4.1.1.15 GABA aminotransferase, EC 2.6.1.19 and succinic semialdehyde dehydrogenase, ECl.2.1.16.

The addition of malonate, a specific inhibitor of the succinic dehydrogenase system, inhibits the regeneration of oxalacetic acid and results in the accumulation of citric, a-ketoglutaric and succinic acids. Upon exhaustion of the remaining stores of oxalacetic acid, pyruvate oxidation in muscle ceases and can only be resumed after further addition of oxalacetic acid or addition of any dicarboxylic acid capable of conversion to oxalacetic acid. Under these conditions, the amount of pyruvate oxidized is equivalent to the amount of oxalacetate supplied. 

Malonic acid is a classical example of a true competitive inhibitor. Malonic acid inhibits succinic dehydrogenase, which catalyzes the oxidation of succinic acid to fumaric acid, as shown below. 

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