Electron carriers, flavin coenzymes

Role as Acyl Carrier and Electron Carrier Flavin Coenzymes (Figure 14.7, Figure 14.8)... 

Flavin Coenzymes Are Electron Carriers in Oxidoreduction Reactions... 

We next focus on the use of fixed-site cofactors and coenzymes. We note that much of this coenzyme chemistry is now linked to very local two-electron chemistry (H, CH3", CH3CO-, -NH2,0 transfer) in enzymes. Additionally, one-electron changes of coenzymes, quinones, flavins and metal ions especially in membranes are used very much in very fast intermediates of twice the one-electron switches over considerable electron transfer distances. At certain points, the chains of catalysis revert to a two-electron reaction (see Figure 5.2), and the whole complex linkage of diffusion and carriers is part of energy transduction (see also proton transfer and Williams in Further Reading). There is a variety of additional coenzymes which are fixed and which we believe came later in evolution, and there are the very important metal ion cofactors which are separately considered below. 

All the internal monooxygenases that have so far been purified and characterized contain flavin coenzymes. The external hydrogen donors include reduced NAD, reduced NADP, ascorbic acid and sulfhydryl compounds. Cofactors required for the external monooxygenases are flavin, pteridine, copper, nonheme iron and heme as cytochrome P-450. In some monooxygenase reactions, enzymes and/or electron carrier systems other than monooxygenase itself are involved in the transfer of an electron or hydrogen from the external hydrogen donor to the cofactor involved. 

The combined dehydrogenation and decarboxylation of pyruvate to the acetyl group of acetyl-CoA (Fig. 16-2) requires the sequential action of three different enzymes and five different coenzymes or prosthetic groups—thiamine pyrophosphate (TPP), flavin adenine dinucleotide (FAD), coenzyme A (CoA, sometimes denoted CoA-SH, to emphasize the role of the —SH group), nicotinamide adenine dinucleotide (NAD), and lipoate. Four different vitamins required in human nutrition are vital components of this system thiamine (in TPP), riboflavin (in FAD), niacin (in NAD), and pantothenate (in CoA). We have already described the roles of FAD and NAD as electron carriers (Chapter 13), and we have encountered TPP as the coenzyme of pyruvate decarboxylase (see Fig. 14-13). 

In contrast to the flavin oxidases, flavin dehydrogenases pass electrons to carriers within electron transport chains and the flavin does not react with 02. Examples include a bacterial trimethylamine dehydrogenase (Fig. 15-9) which contains an iron-sulfur duster that serves as the immediate electron acceptor167 169 and yeast flavocytochrome b2, a lactate dehydrogenase that passes electrons to a built-in heme group which can then pass the electrons to an external acceptor, another heme in cytochrome c.170-173 Like glycolate oxidase, these enzymes bind their flavin coenzyme at the ends of 8-stranded a(i barrels similar... 

The cytochromes are the electron carrier heme proteins occurring in the mitochondrial respiratory chain.449 There are five cytochromes linking coenzymes Q (ubiquinone) and 02 in this electron transport chain (Scheme 7). Cytochromes are also involved in energy transfer in photosynthesis. The iron atom in cytochromes cycles between the Fe11 and Fe111 states, i.e. they are one-electron carriers, in contrast to CoQ and the NADH flavins they act upon which are two-electron carriers. Thus, one molecule of reduced CoQ transfer its two high potential electrons to two molecules of cytochrome b, the next member of the electron transport chain. 

The metabolic function of the flavin coenzymes is as electron carriers in a wide variety of oxidation and reduction reactions central to aU metabolic processes, including the mitochondrial electron transport chain. Unlike the nicotinamide nucleotide coenzymes (Section 8.4.1), which act as cosubstrates, leaving the catalytic site of the enzyme at the end of the reaction, the flavin coenzymes remain bound to the enzyme throughout the catalytic cycle. 

The other major electron carrier in the oxidation of fuel molecules is the coenzyme flavin adenine dinucleotide (Figure 14.14). The abbreviations for the oxidized and reduced forms of this carrier are FAD and FADH2, respectively. FAD is the electron acceptor in reactions of the type... 

Oxidation of pyruvate and fatty acids to CO2 coupled to reduction of NAD to NADH and of flavin adenine dinucleotide (FAD), another oxidized electron carrier, to its reduced form, FADH2 (see Figure 2-26). These electron carriers are often referred to as coenzymes. NAD, NADH, FAD, and FADH2 are diffusible and not permanently bound to proteins. Most of the reactions occur in the matrix two are catalyzed by inner-membrane enzymes that face the matrix. 

Each complex contains one or more electron-carrying prosthetic groups iron-sulfur clusters, flavins, heme groups, and copper ions (see Table 8-2). Cytochrome c, which contains heme, and coenzyme Q (CoQ) are mobile electron carriers. 

FMN, also known as riboflavin phosphate, is a flavin containing electron carrier in the cell (Figure 14.7). It participates in oxidation/ reduction reactions and, like FAD, differs from the nicotinamide coenzymes (NAD+ and NADP ) in being able to accept electrons either singly or in pairs (Figure 14.8). NAD+ and NADP+ can only accept electrons in pairs. 

Flavin adenine dinucleotide (FAD) is the other major electron carrier in the oxidation of fuel molecules. This coenzyme is a derivative of ADP and the vitamin riboflavin. The reactive site is located within the riboflavin ring systan (see I Figure 12.19). 

The first electron carrier in the electron transport chain is an enzyme that contains a tightly bound coenzyme. The coenzyme has a structure similar to FAD. The enzyme formed by the combination of this coenzyme with a protein is called flavin mononucleotide (FMN). Two electrons and one ion from NADH plus another H ion from a mitochondrion pass to FMN, then to an iron-sulfur (Fe—S) protein, and then to coenzyme Q (CoQ). CoQ is also the entry point into the electron transport chain for the two electrons and two H ions from FADH2. As NADH and FADH2 release their hydrogen atoms and electrons, NAD and FAD are regenerated for reuse in the citric acid cycle. 

There are many carrier molecules for electrons one is called the nicotinamide adenine dinucleotide (NAD ) and another is the flavin adenine dinucleotide (FAD ). The reduced cofactors NADH and FADH2 transfer electrons to the electron transport chain. Flavin mononucleotide receives electrons from NADH and passes them to coenzyme Q through Fe-S systems. Coenzyme Q receives electrons from flavin mononucleotide and FADH2 through Fe-S systems. Cytochromes receive electrons from the reduced form of coenzyme Q. Each cytochrome consists of a heme group, and the iron of the heme group is reduced when the cytochrome receives an electron Fe + Fe " ". At the end of the electron transfer chain, oxygen is reduced to water. 

The mitochondrial electron transport chain is a series of enzymes and coenzymes in the crista membrane, each of which is reduced by the preceding coenzyme, and in turn reduces the next, until finally the protons and electrons that have entered the chain from either NADH or reduced flavin reduce oxygen to water. The sequence of the electron carriers shown in Figure 3.17 has been determined in two ways ... 

Keilin soon realized that three of the absorption bands, those at 604,564, and 550 nm (a, b, and c), represented different pigments, while the one at 521 nm was common to all three. Keilin proposed the names cytochromes a, b, and c. The idea of an electron transport or respiratory chain followed6 quickly as the flavin and pyridine nucleotide coenzymes were recognized to play their role at the dehydrogenase level. Hydrogen removed from substrates by these carriers could be used to oxidize reduced cytochromes. The latter would be oxidized by oxygen under the influence of cytochrome oxidase. 

Flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN) are also carriers of electrons and have related chemical structures (Fig. 5). Both of these coenzymes consist of a flavine mononucleotide unit which contains the reactive... 

In all these reactions, the flavin nucleotide combines with a protein to form a flavoprotein. In the reactions involved in electron transport, the flavoprotein acts as a hydrogen carrier and plays an important role in the transfer of electrons from pyridine nucleotides to cytochromes. Among the flavoproteins of interest in the electron transport chain are (1) coenzyme 1-diaphorase, (2) the Warburg flavoprotein, (3) NADH cytochrome c reductase, (4) NADPH cytochrome c reductase, (5) NADH cytochrome reductase, (6) NADH 2-methyl-l,4maphthoquinone reductase, and (7) succinic cytochrome c reductase. The most important among these are succinic cytochrome c reductase and NADH cytochrome c reductase. The following discussion of these two flavoproteins may serve as an example for the others. 

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