Nqq

Fumarate

FAD FADH2

Fumarate

FIGURE 20.14 • The succinate dehydrogenase reaction. Oxidation of succinate occurs with reduction of [FAD]. Reoxidation of [FADH2] transfers electrons to coenzyme Q.

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.

Histidine

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.

Cys_

FIGURE 20.16 • The Fe2S2 cluster of succi-nate dehydrogenase.

20.9 • Succinate Dehydrogenase—An Oxidation Involving FAD

The oxidation of succinate to fumarate (Figure 20.14) is carried out by succi-nate dehydrogenase, a membrane-bound enzyme that is actually part of the electron transport chain. As will be seen in Chapter 21, succinate dehydrogenase is part of the succinate-coenzyme Q reductase of the electron transport chain. In contrast with all of the other enzymes of the TCA cycle, which are soluble proteins found in the mitochondrial matrix, succinate dehydrogenase is an integral membrane protein tightly associated with the inner mitochon-drial membrane. Succinate oxidation involves removal of H atoms across a C—C bond, rather than a C—O or C—N bond, and produces the trans-unsaturated fumarate. This reaction (the oxidation of an alkane to an alkene) is not sufficiently exergonic to reduce NAD+, but it does yield enough energy to reduce [FAD]. (By contrast, oxidations of alcohols to ketones or aldehydes are more energetically favorable and provide sufficient energy to reduce NAD+.) This important point is illustrated and clarified in an example in Chapter 21.

Succinate dehydrogenase is a dimeric protein, with subunits of molecular masses 70 kD and 27 kD (see Table 20.1). FAD is covalently bound to the larger subunit; the bond involves a methylene group of C-8a of FAD and N-3 of a histidine on the protein (Figure 20.15). Succinate dehydrogenase also contains three different iron-sulfur clusters (Figure 20.16). Viewed from either end of the succinate molecule, the reaction involves dehydrogenation a,¡3 to a car-bonyl (actually, a carboxyl) group. The dehydrogenation is stereospecific (Figure 20.14), with the pro-S hydrogen removed from one carbon atom and the pro-R hydrogen removed from the other. The electrons captured by [FAD] in this reaction are passed directly into the iron-sulfur clusters of the enzyme and on to coenzyme Q(UQ). The covalently bound FAD is first reduced to [FADH2] and then reoxidized to form [FAD] and the reduced form of coenzyme Q, UQH2. Electrons captured by UQH2 then flow through the rest of the electron transport chain in a series of events that is discussed in detail in Chapter 21.

Note that flavin coenzymes can carry out either one-electron or two-electron transfers. The succinate dehydrogenase reaction represents a net two-electron reduction of FAD.

20.10 • Fumarase Catalyzes Tmras-Hydration of Fumarate

Fumarate is hydrated in a stereospecific reaction by fumarase to give L-malate (Figure 20.17). The reaction involves trans-addition of the elements of water across the double bond. Recall that aconitase carries out a similar reaction,

Was this article helpful?

0 0

Post a comment