Enzymes succinic dehydrogenase, activity

The enzyme succinate dehydrogenase (SDH) is competitively inhibited by malo-nate. Figure 14.14 shows the structures of succinate and malonate. The structural similarity between them is obvious and is the basis of malonate s ability to mimic succinate and bind at the active site of SDH. However, unlike succinate, which is oxidized by SDH to form fumarate, malonate cannot lose two hydrogens consequently, it is unreactive. 

Because the metabolism of DEHP was catalyzed by so many fractions of the trout liver homogenate, these fractions were characterized by measurement of marker enzymes to determine which organelles actually were responsible for the observed DEHP metabolism. Succinic dehydrogenase activity was used as a marker for mitochondria, whereas glucose-6-phosphatase was used as a marker for microsomes. The distribution of DEHP oxidase activity (production of polar metabolites 1 and 2 with added NADPH) and of DEHP esterase activity (production of monoester without added NADPH) were also determined. It was found (Figure 2) that the distribution of DEHP oxidase activity parallels the distribution of microsomal activity and the distribution of DEHP esterase activity parallels the distribution of microsomal activity, but is also present in the cytosol fraction. 

As described elsewhere in this chapter, alterations in the activity of a number of lung enzymes have been described after acute and chronic ozone exposure. With the possible exceptions of the sulfhydryl-containing enzyme succinic dehydrogenase and the cytochrome P-4 en me benzopyrene hydroxylase, it is difficult to determine whether these findings are due to a direct oxidative effect of ozone or are secondary to changes in protein synthesis, concentrations of intermediates, or destruction of cells or organelles. 

Hazel, J.R. (1972). The effect of temperature acclimation upon succinic dehydrogenase activity from the muscle of common goldfish lipid reactivation of the soluble enzyme. Comparative Biochemistry and Physiology 43B, 863-882. 

The succinate dehydrogenase of S. acidocaldarius (DSM 639) is located in the cytoplasmic and membrane fractions when cells are disrupted either by sonication or decompressive disruption. About 10-30% of the activity is associated with the membrane fraction [30]. The purified membrane-bound succinate dehydrogenase activity (M, 141 000) consists of four subunits (Mr 66000, 31 000, 28 000, and 12,800). The enzyme contains a covalently-bound flavin as well as iron and acid-labile sulfide but no cytochrome [111]. The dehydrogenase reduces the following acceptors (listed in order of decreasing... 

There were two clearly separated peaks, C and D, sedimenting at 1.2 M and 1.3 M-sucrose (Fig. 2). Examination by the electron microscope showed them both to have the morphological characteristics of synaptosomes. It is well established that a good enzyme marker for intact synaptosomes is occluded lactic dehydrogenase (L-lactate NAD oxidoreductase, EC 1.1.1.27) (Marchbanks, 1967), a component of the cell sap. As can be seen in Table I, 83 % of the occluded form of the enzyme of the original P2 fraction is shared between peaks C and D. Both also contained succinic dehydrogenase activity owing to the presence of intraterminal mitochondria. The membrane marker acetylcholinesterase (acetylcholine hydrolase, EC 3.1.1.7) was also present in these peaks and was notably absent from the mitochondrial and lysosomal fractions (Table I). 

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. 

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

The last of Hopkins many contributions to biochemistry was the demonstration that an enzyme—succinic dehydrogenase—was dependent for its activity on free SH groups in its structure (Hopkins et al., 1938). He used alloxan to oxidize the SH and inactivate the enzyme, and showed that glutathione (GSH) provided partial protection for the enzyme by reducing the alloxan. Then, from Glasgow, came the unexpected discovery that injected alloxan caused intense hypoglycemia in rabbits, followed by necrosis of the beta cells in the islets of Langerhans of the pancreas (Shaw Dunn et al., 1943). 

A variety of oxidative enzymes in the pars intermedia of the pig have been demonstrated by Howe and Thody (1967). The epithelial cells of the pars intermedia of the ox showed a strong positive reaction for cytochrome oxidase, but it was not possible to differentiate between type 1 and type II cells (Raftery 1969). Sections treated with 0.05 M sodium azide as inhibitor were negative. The strong reaction for the mitochondria-associated enzymes, succinic dehydrogenase and cytochrome oxidase, indicates high oxidative activity within the cells of the intermedia. 

The orderly functioning of the enzyme systems in mitochondria is dependent upon the structural organization of the mitochondria, for de Robertis et alP find that any treatment which causes dissolution of the mitochondria (e.g., freezing) greatly reduces the succinic dehydrogenase activity and oxygen uptake of cells. 

Although the dextro and levo forms are comparable in toxicity for mice, the levo isomer shows hi er biological activity.to vitro studies indicate that tetramisole causes muscular paralysis in ascaris worms. Specifically, the drug inhibits succinate dehydrogenase activity of the worm. The levo isomer is a more potent enzyme inhibitor than the dextro isomer or the racemic mixture. 

Competitive inhibitors bind at the substrate-binding site, that is, they compete with the substrate for the active site. In pure competitive inhibition, the inhibitor is assumed to bind to the free enzyme but not to the enzyme-substrate (ES) complex. 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 structurally the substrate. As an example, we can mention malonate, which is an inhibitor for dehydrogenation of succinate of an enzyme-succinic dehydrogenase and resembles the structure of succinate (Fig. 6.36)... 

Figure 4. The citrate cycle. There is complete oxidation of one molecule of acetyl-CoA for each turn of the cycle CH3COSC0A + 2O2 - 2CO2 + H2O + CoASH. The rate of the citrate cycle is determined by many factors including the ADP/ATP ratio, NAD7NADH ratio, and substrate concentrations. During muscle contraction, Ca is released from cellular stores (mainly the sarcoplasmic reticulum) and then taken up in part by the mitochondria (see Table 2). Ca " activates 2-oxoglutarate and isocitrate dehydrogenases (Brown, 1992). Succinate dehydrogenase may be effectively irreversible. Enzymes ...

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