Histidine residues succinate dehydrogenase

FAD is bound covalently to the enzyme protein through a specific histidine residue. Succinate dehydrogenase is tightly bound to the mitochondrial inner membrane. The importance of this binding is that the reduced flavin, which must be reoxidized for the enzyme to act again, becomes reoxidized through interaction with the mitochondrial electron transport system, also bound to the membrane. 

FIGURE 20.15 The covalent bond between FAD and succinate dehydrogenase involves the C-8a methylene group of FAD and the N-3 of a histidine residue on the enzyme. 

Complex II is perhaps better known by its other name—succinate dehydrogenase, the only TCA cycle enzyme that is an integral membrane protein in the inner mitochondrial membrane. This enzyme has a mass of approximately 100 to 140 kD and is composed of four subunits two Fe-S proteins of masses 70 kD and 27 kD, and two other peptides of masses 15 kD and 13 kD. Also known as flavoprotein 2 (FP2), it contains an FAD covalently bound to a histidine residue (see Figure 20.15), and three Fe-S centers a 4Fe-4S cluster, a 3Fe-4S cluster, and a 2Fe-2S cluster. When succinate is converted to fumarate in the TCA cycle, concomitant reduction of bound FAD to FADHg occurs in succinate dehydrogenase. This FADHg transfers its electrons immediately to Fe-S centers, which pass them on to UQ. Electron flow from succinate to UQ,... 

At the active site of beef heart mitochondrial succinate dehydrogenase (EC 1.3.99.1), the FAD is covalently linked by C-8a to nitrogen of a histidine residue (Fig. 2b) [20]. In the catalytic reaction, removal of a proton from C-3 of the succinate may be followed by attack of the 3-carbanion on N-5 of the FAD to form an intermediate adduct, which breaks down with loss of a proton from C-2 of the succinate, giving fumarate and a reduced FAD moiety [21]. This mechanism is not certain, but it is established that the succinate loses two non-equivalent hydrogen atoms by a trans elimination (Fig. 4) [22], In other enzymes, different types of covalent attachment of the FAD are known [23]. 

It is important to note that as shown in Scheme 9.105 one pro-R and one pro-S hydrogen are removed during the conversion of succinate to fumerate (FAD to FADH2) and that the cofactor to the sucdnate dehydrogenase, that is, FAD, appears to be bound to a histidine residue (Chapter 12) on the enzyme through (what was)... 

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