Prosthetic groups, succinate dehydrogenase

PropUtrabacUrium arabinosum, -gly-cerophosphate dehydrogenase of, 260 2-Propyn-l-ol, catalase and, 404 Prostaglandin, biosynthesis, 168 Prosthetic groups, succinate dehydrogenase, 234-235... 

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. 

This complex consists of four subunits, all of which are encoded on nuclear DNA, synthesized on cytosolic ribosomes, and transported into mitochondria. The succinate dehydrogenase (SDH) component of the complex oxidizes succinate to fumarate with transfer of electrons via its prosthetic group, FAD, to ubiquinone. It is unique in that it participates both in the respiratory chain and in the tricarboxylic acid (TC A) cycle. Defects of complex II are rare and only about 10 cases have been reported to date. Clinical syndromes include myopathy, but the major presenting features are often encephalopathy, with seizures and psychomotor retardation. Succinate oxidation is severely impaired (Figure 11). 

The oxygen reactivity of flavohydroquinone bound to apoflavoprotein dehydrogenases can vary considerably from fast (flavodoxins), moderate (xanthine oxidase) to nil (succinate dehydrogenase) Most, but not all, flavoprotein dehydrogenases contain one or more types of metal prosthetic groups, e.g. xanthine oxidase contains also Fe and Mo. Since these metal ions are involved in electron flux, their possible participation in the reaction with O2 cannot be excluded. Much evidence, however, indicates that the flavin is involved in the one-electron reduction of Oj, as shown in Equation (5). 

Singer, T.P. Johnson, M.K. (1985) The prosthetic groups of succinate dehydrogenase 30 years from discovery to identification. 

Mitochondrial succinate dehydrogenase, which catalyzes the reaction of Eq. 15-21, contains a flavin prosthetic group that is covalently attached to a histidine side chain. This modified FAD was isolated and identified as 8a-(Ne2-histidyl)-FAD 219 The same prosthetic group has also been found in several other dehydrogenases.220 It was the first identified member of a series of modified FAD or riboflavin 5 -phosphate derivatives that are attached by covalent bonds to the active sites of more than 20 different enzymes.219... 

Enzymes. Heme serves as the prosthetic group lor catalase, peroxidase, cytochrome oxidase, and the related cytochromes. Catalase and peroxidase iron are presumably present in the ferric form while the iron of Ihe cytochromes may exist in Ihe reduced or oxidized lorni. A number of tlasoproteins. including succinic dehydrogenase, contain iron in ihe molecule. Iron appears to act as coeiuyme for aeonilase. A number of other enzymes require the presence of iron for their activities,... 

The dehydrogenases that remove electrons from succinate or NADH contain flavins as prosthetic groups. NADH... 

The electron carriers in the respiratory assembly of the inner mitochondrial membrane are quinones, flavins, iron-sulfur complexes, heme groups of cytochromes, and copper ions. Electrons from NADH are transferred to the FMN prosthetic group of NADH-Q oxidoreductase (Complex I), the first of four complexes. This oxidoreductase also contains Fe-S centers. The electrons emerge in QH2, the reduced form of ubiquinone (Q). The citric acid cycle enzyme succinate dehydrogenase is a component of the succinate-Q reductase complex (Complex II), which donates electrons from FADH2 to Q to form QH2.This highly mobile hydrophobic carrier transfers its electrons to Q-cytochrome c oxidoreductase (Complex III), a complex that contains cytochromes h and c j and an Fe-S center. This complex reduces cytochrome c, a water-soluble peripheral membrane protein. Cytochrome c, like Q, is a mobile carrier of electrons, which it then transfers to cytochrome c oxidase (Complex IV). This complex contains cytochromes a and a 3 and three copper ions. A heme iron ion and a copper ion in this oxidase transfer electrons to O2, the ultimate acceptor, to form H2O. 

The flavin prosthetic groups of NADH dehydrogenase and succinate dehydrogenase face the M side of the membrane ... 

Llavin adenine dinucleotide (PAD) is a prosthetic group that participates in several intracellular oxidation-reduction reactions. During the catalytic cycle of the enzyme succinate dehydrogenase, PAD accepts two electrons from succinate, yielding fumarate as a prodnct. Becanse PAD is tightly bound to the enzyme, the reaction is sometimes shown this way... 

The prosthetic group of succinic dehydrogenase is a ferroflavoprotein containing one flavin molecule and four iron atoms. The overall molecule is rather large and has a molecular weight of 200,000. As early as 1939, Keilin and Hartree observed that the addition of succinate to a succinic dehydrogenase preparation... 

Riboflavin is an important constituent of the flavoproteins.The prosthetic group of these compound proteins contains riboflavin in the form of the phosphate (flavin mononucleotide, FMN) or in a more complex form as flavin adenine dinucleotide (FAD). There are several flavoproteins that function in the animal body they are all concerned with chemical reactions involving the transport of hydrogen. Further details of the importance of flavoproteins in carbohydrate and amino acid metabolism are discussed in Chapter 9. Flavin adenine dinucleotide plays a role in the oxidative phosphorylation system (see Fig. 9.2 on p. 196) and forms the prosthetic group of the enzyme succinic dehydrogenase, which converts succinic acid to fumaric acid in the citric acid cycle. It is also the coenzyme for acyl-CoA dehydrogenase. 

Although most electrons are fed into the respiratory chain via NAD some dehydrogenases bypass NAD and feed them in at the level of ubiquinone. The membrane-bound enzyme succinate dehydrogenase which catalyses the oxidation of succinate to fumarate in the citrate cycle contains flavin adenine dinucleotide (FAD) (page 244) as its prosthetic group and operates in this way. 

In the first of these three reactions two hydrogen atoms are removed from succinate and fumarate is formed. In this dehydrogenation the hydrogen acceptor is not NAD but a flavo-protein (FF). The flavoprotein is in fact the enzyme succinate dehydrogenase which contains flavin adenine dinucleotide (FAD) as a covalently bound prosthetic group and also non-haem iron. It differs from other enzymes of the citrate cycle in being an integral constituent of the inner mitochondrial membrane and directly linked to the electron-transport chain. 

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