Succinate dehydrogenase mammalian

Covalently Bound Flavins. The FAD prosthetic group in mammalian succinate dehydrogenase was found to be covalently affixed to protein at the 8 a-position through the linkage of 3-position of histidine (102,103). Since then, several covalently bound riboflavins (104,105) have been found successively from the en2ymes Hsted in Table 3. The biosynthetic mechanism, however, has not been clarified. 

The functions of the heme is uncertain. The soluble mammalian succinate dehydrogenase resembles closely that of E. coli and contains three Fe-S centers binuclear SI of E° 0 V, and tetranuclear S2 and S3 of -0.25 to -0.40 and + 0.065 V, respectively. Center S3 appears to operate between the -2 and -1 states of Eq. 16-17 just as does the cluster in the Chromatium high potential iron protein. The function of the very low potential S2 is not certain, but the following sequence of electron transport involving SI and S3 and the bound ubiquinone QD-S66 has been proposed (Eq. 18-4). 

Both the membrane-bound and the soluble succinate dehydrogenases are capable of catalyzing fumarate reduction in the presence of a suitable electron donor such as FMNHa. In the mammalian enzyme, this activity is not more than a few percent of the succinate-PMS reductase activity (23, 25). Ringler and Singer (177) have also shown that in brain mito-... 

The succinate dehydrogenase of yeast mitochondria was isolated by Singer et al. 15, 219) in 1957, and stated to have a molecular weight of 200,000 and an iron flavin ratio of 4 1, similar to the mammalian enzyme. These studies antedated, however, the purification of mammalian succinate dehydrogenase by Davis and Hatefi. Therefore, the exact molecular weight and composition of the yeast enzyme will have to be reexamined in light of present information. 

A very interesting observation is that the R. rubrum succinate dehydrogenase can cross-interact with alkali-inactivated mammalian respiratory... 

The FAD-requiring enzymes in mammalian systems include the D- and L-amino acid oxidases, mono- and diamine oxidases, glucose oxidase, succinate dehydrogenase, a-glycerophosphate dehydrogenase, and glutathione reductase. FMN is a cofactor for renal L-amino acid oxidase, NADH reductase, and a-hydroxy acid oxidase. In succinate dehydrogenase, FAD is linked to a histidyl residue in liver mitochondrial monoamine oxidase, to a cysteinyl residue. In other cases, the attachment is nonco-valent but the dissociation constant is very low. 

The formation of succinate from fumarate by fumarate reductase (FR) and anaerobic phosphorylation of ADP to ATP are amongst the important reactions taking place in the mitochondria to provide energy to the helminths. The FR system of helminths differs from succinate dehydrogenase (SDH) of mammalian tissues in several ways. For example (a) FR requires NAD while SDH utilizes flavin nucleotide (FAD) as the coenzyme (b) FR acts only in one direction but SDH is a reversible enzyme (c) FR acts as the terminal electron acceptor under anaerobic conditions while SDH has no such property. Levamisole was shown to inhibit the FR in Ascaris [43]. 

The metabolic steps in gluconeogenesis occur in two intracellular compartments (Fig. 3.2) the cytosol and the mitochondrial matrix. The enzymes of the tricarboxylic acid cycle reside in the mitochondrial matrix, apart from succinate dehydrogenase which is present in the inner mitochondrial membrane, whereas most of the enzymes of the gluconeogenic pathway are present in the cytosol. Transaminases, such as alanine aminotransferase and aspartate aminotransferase, are present both in mitochondria and cytosol of the domestic fowl liver (Sarkar, 1977). One of the control enzymes in gluconeogenesis, PEPCK, has a different intracellular distribution in avian liver compared with mammalian liver (Table 3.3). PEPCK in both pigeon and domestic fowl liver is present almost exclusively (> 99%) in mitochondria (Soling et al.. 1973), whereas in most mammals that have been studied, it is present mainly in the cytosol, and only present, if at all, in smaller amounts in... 

Cholesterol, in various proportions, is a natural constituent of mammalian plasma membranes but, if the proportion is allowed to increase, membrane function is usually diminished. Thus the membrane that surrounds the sarcoplasmic reticulum vesicles in muscle progressively loses the calcium-transporting function of its ATPase when cholesterol starts replacing the phospholipids. Similarly, ox-heart mitochondria, when exposed to cholesterol, progressively lose the activity of ATPase, succinate dehydrogenase, and /3-hydroxybutyrate dehydrogenase (Warren et aL, 1975). 

More than 100 years ago a fluorescent compound was isolated first fi om whey, and later from different biological materials. When it Ijecame clear that the isolated yellow pigments, named lactochrome, ovoflavin, or lactoflavin, had a common structure, the new compound was named riboflavin (vitamin B2) (for historical review see 2). In the years between 1933 and 1935 the structure and the main chemical reactions of riboflavin were studied and the chemical synthesis was performed. Soon afterward, the coenzyme forms, flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), were isolated in pure form, and the structures were determined. In the last 50 years many flavoproteins were isolated and their physicochemical properties were studied. Succinate dehydrogenase was the first enzyme found with the prosthetic group (FAD) covalently bound to the protein. About 20 flavoproteins are now known to contain covalently bound coenzyme (mainly via carbon atom 8a) (3). In mammalian tissue, the number of covalently bound flavoproteins appears to be limited. 

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