Coenzyme oxidation reaction

FIGURE 24.11 The acyl-CoA dehydrogenase reaction. The two electrons removed in this oxidation reaction are delivered to the electron transport chain in the form of reduced coenzyme Q (UQH9). 

The third reaction of this cycle is the oxidation of the hydroxyl group at the /3-position to produce a /3-ketoacyl-CoA derivative. This second oxidation reaction is catalyzed by L-hydroxyacyl-CoA dehydrogenase, an enzyme that requires NAD as a coenzyme. NADH produced in this reaction represents metabolic energy. Each NADH produced in mitochondria by this reaction drives the synthesis of 2.5 molecules of ATP in the electron transport pathway. L-Hydroxyacyl-... 

In some cases, enzymes require the assistance of coenzymes (cofactors) to ensure the reactions proceed. Coenzymes include vitamins, metal ions, acids, and bases. They can act as transporters or electron acceptors or be involved in oxidation-reduction reactions. At the completion of the reaction, coenzymes are released, and they do not form part of the products. For some reactions that are energetically unfavorable, an energy source provided by the compound adenosine triphosphate (ATP) is needed to ensure the reactions proceed, as shown in the following reactions ... 

FAD is a coenzyme for a large number of oxidation reactions, largely of carbohydrates. Correspondingly, FADH2 is a coenzyme for a number of reduction reactions. Certain of the reactions of FAD and FADH2 are involved in the electron transport chain in mitochondria, associated with the synthesis of ATP. We shall see examples in chapter 17. 

NMN is basically half of the NAD+ molecule nicotinamide ribose phosphate. NADP+ is NAD+ bearing a phosphate group at C3 of the ribose group attached to the adenine. The redox chemistry is the same in all three forms of the coenzymes. NAD+ is the form most frequently employed for biochemical oxidation reactions in catabohsm and NADP+ (in its reduced form NADPH) is the form usually employed for biochemical reduction reactions in anabohsm. NMN is employed infrequently. 

The synthesis pathway of quinolizidine alkaloids is based on lysine conversion by enzymatic activity to cadaverine in exactly the same way as in the case of piperidine alkaloids. Certainly, in the relatively rich literature which attempts to explain quinolizidine alkaloid synthesis °, there are different experimental variants of this conversion. According to new experimental data, the conversion is achieved by coenzyme PLP (pyridoxal phosphate) activity, when the lysine is CO2 reduced. From cadeverine, via the activity of the diamine oxidase, Schiff base formation and four minor reactions (Aldol-type reaction, hydrolysis of imine to aldehyde/amine, oxidative reaction and again Schiff base formation), the pathway is divided into two directions. The subway synthesizes (—)-lupinine by two reductive steps, and the main synthesis stream goes via the Schiff base formation and coupling to the compound substrate, from which again the synthetic pathway divides to form (+)-lupanine synthesis and (—)-sparteine synthesis. From (—)-sparteine, the route by conversion to (+)-cytisine synthesis is open (Figure 51). Cytisine is an alkaloid with the pyridone nucleus. 

Following removal of one acetyl-CoA unit from palmitoyl-CoA, the coenzyme A thioester of the shortened fatty acid (now the 14-carbon myristate) remains. The myristoyl-CoA can now go through another set of four /3-oxidation reactions, exactly analogous to the first, to yield a second molecule of acetyl-CoA and lauroyl-CoA, the coenzyme A thioester of the 12-carbon laurate. Altogether, seven passes through the j8-oxidation sequence are required to oxidize one molecule of palmitoyl-CoA to eight molecules of acetyl-CoA (Fig. 17-8b). The overall equation is... 

The product of this metabolic sequence, pyruvate, is a metabolite of caitral importance. Its fate depends upon the conditions within a cell and upon the type of cell. When oxygen is plentiful pyruvate is usually converted to acetyl-coenzyme A, but under anaerobic conditions it may be reduced by NADH + H+ to the alcohol lactic acid (Fig. 10-3, step h). This reduction exactly balances the previous oxidation step, that is, the oxidation of glycer-aldehyde 3-phosphate to 3-phospho-glycerate (steps a and b). With a balanced sequence of an oxidation reaction, followed by a reduction reaction, glucose can be converted to lactate in the absence of oxygen, a fermentation process. The lactic acid fermentation occurs not only in certain bacteria but also in our own muscles under conditions of extremely vigorous exercise. It also occurs continuously in some tissues, e.g., the transparent lens and cornea of the eye. 

The dehydrogenation of an alcohol to a ketone or aldehyde (Eq. 15-1) is one of the most frequent biological oxidation reactions. Although the hydrogen atoms removed from the substrate are often indicated simply as 2[H], it was recognized early in the twentieth century that they are actually transferred to hydrogen-carrying coenzymes such as NAD+, NADP+, FAD, and riboflavin... 

Three facts account for the need of cells for both the flavin and pyridine nucleotide coenzymes (1) Flavins are usually stronger oxidizing agents than is NAD+. This property fits them for a role in the electron transport chains of mitochondria where a sequence of increasingly more powerful oxidants is needed and makes them ideal oxidants in a variety of other dehydrogenations. (2) Flavins can be reduced either by one- or two-electron processes. This enables them to participate in oxidation reactions involving free radicals and in reactions with metal ions. (3) Reduced flavins... 

First isolated from human urine, biopterin (Fig. 15-17) is present in liver and other tissues where it functions in a reduced form as a hydroxylation coenzyme (see Chapter 18).338 It is also present in nitric oxide synthase (Chapter 18).341/342 Other functions in oxidative reactions, in regulation of electron transport, and in photosynthesis have been proposed.343 Neopterin, found in honeybee larvae, resembles biopterin but has a D-erythro configuration in the side chain. The red eye pigments of Drosophila, called drosopterins, are complex dimeric pterins containing fused 7-membered rings (Fig. 15-17).344 345... 

Oxidation-reduction reactions coenzymes of 765 - 827 Oxidative decarboxylation of a-oxoacids 511, 736, 796-802... 

Elimination of P from 5-enolpyruvylshikimate 3-P (Eq. 25-3 and Fig. 25-1, step g) produces chorismate.30 The 24-kDa chorismate synthase, which catalyzes this reaction, requires for activity a reduced flavin. Although there is no obvious need for an oxidation reduction coenzyme, there is strong evidence that the flavin may play an essential role in catalysis, perhaps via a radical mechanism.31-331 ... 

These oxidation reactions employing pyridine nucleotides and flavoproteins are especially important in primary metabolism in liberating energy from fuel molecules in the form of ATP. The reduced coenzymes formed in the process are normally reoxidized via the electron transport chain... 

In fact, the a-ketoglutarate/glutamate dehydrogenase is a generally applicable method for the regeneration of NAD and NADP in laboratory scale productions. Both components involved are inexpensive and stable. Quite recently, a method for the oxidation of the reduced nicotinamide coenzymes based on bacterial NAD(P)H oxidase has been described [225], This enzyme oxidizes NADH as well as NADPH with low Km values. The product of this reaction is peroxide, which tends to deactivate enzymes, but it can be destroyed simultaneously by addition of catalase. The irreversible peroxide/catalase reaction favours the ADH catalyzed oxidation reaction, and complete conversions of this reaction type are described. 

Some enzymes require additional chemical species, called cofactors or coenzymes, to be fully active. Cofactors include metal ions such as Fe+2, Zn+2, and Cu+2. Coenzymes are organic molecules that allow transfer of functional groups or reduction/oxidation reactions. Examples include thiamine pyrophosphate (4.6) and pyridoxine 5 -phosphate (4.7) (Figure 4.8). 

The same factors discussed in the previous section as being important for biocatalytic reactions in general apply to biocatalytic oxidation reactions as well. In addition, however, another aspect of biocatalysts becomes important the use of cofactors or coenzymes. Many enzymes function with the help of a specific cofactor, a small non-protein organic or metallo-organic group that is capable of facilitating the reaction to be performed. Enzymes that catalyze oxidation re-... 

Examples of some cofactors (coenzymes) frequently used in biocatalytic oxidation reactions and enzymes using these cofactors... 

Utilized pathway differs by bacterium, though NADP as well as NAD is the coenzyme participating in the reduction-oxidation reaction of organic substance and also has the structural resemblance. It is, therefore, not too much to say that the glycolytic pathway of the bacteria producing hydrogen by NADH pathway is the EM pathway (Figure 4). 

At the E3 active site, the lipoamide is oxidized by coenzyme FAD. The reactivated lipoamide is ready to begin another reaction cycle. 

The answer is b. (Murray, pp 627-661. Scriver, pp 3897-3964. Sack, pp 121-138. Wilson, pp 287-320.) Nicotinamide adenine dinucleotide (NAD+) is the functional coenzyme derivative of niacin. It is the major electron acceptor in the oxidation of molecules, generating NADH, which is the major electron donor for reduction reactions. Thiamine (also known as vitamin Bi) occurs functionally as thiamine pyrophosphate and is a coenzyme for enzymes such as pyruvate dehydrogenase. Riboflavin (vitamin B2) functions in the coenzyme forms of flavin mononucleotide (FMN) or flavin adenine dinucleotide (FAD). When concentrated, both have a yellow color due to the riboflavin they contain. Both function as prosthetic groups of oxidation-reduction enzymes or flavoproteins. Flavoproteins are active in selected oxidation reactions and in electron transport, but they do not have the ubiquitous role of NAD+. 

The simplest example of such reactions is the decarboxylation of pyruvate. Both model and enzyme studies have shown the intermediacy of covalent complexes formed between the cofactor and the substrate. Kluger and coworkers have studied extensively the chemical and enzymatic behavior of the pyruvate and acetaldehyde complexes of ThDP (2-lactyl or LThDP, and 2-hydroxyethylThDP or HEThDP, respectively) . As Scheme 1 indicates, the coenzyme catalyzes both nonoxidative and oxidative pathways of pyruvate decarboxylation. The latter reactions are of immense consequence in human physiology. While the oxidation is a complex process, requiring an oxidizing agent (lipoic acid in the a-keto acid dehydrogenases , or flavin adenine dinucleotide, FAD or nicotinamide adenine dinucleotide , NAD " in the a-keto acid oxidases and Fe4.S4 in the pyruvate-ferredoxin oxidoreductase ) in addition to ThDP, it is generally accepted that the enamine is the substrate for the oxidation reactions. 

Tyrosine hydroxylase uses BH4 to activate O,. One oxygen atom is attached to tyrosine s aromatic ring, while the other atom oxidizes the coenzyme. DOPA, the product of the reaction, is used in the synthesis of the other catecholamines. 

In these reactions, the C2-atom of ThDP must be deprotonated to allo v this atom to attack the carbonyl carbon of the different substrates. In all ThDP-dependent enzymes this nucleophilic attack of the deprotonated C2-atom of the coenzyme on the substrates results in the formation of a covalent adduct at the C2-atom of the thiazolium ring of the cofactor (Ila and Ilb in Scheme 16.1). This reaction requires protonation of the carbonyl oxygen of the substrate and sterical orientation of the substituents. In the next step during catalysis either CO2, as in the case of decarboxylating enzymes, or an aldo sugar, as in the case of transketo-lase, is eliminated, accompanied by the formation of an a-carbanion/enamine intermediate (Ilia and Illb in Scheme 16.1). Dependent on the enzyme this intermediate reacts either by elimination of an aldehyde, such as in pyruvate decarboxylase, or with a second substrate, such as in transketolase and acetohydroxyacid synthase. In these reaction steps proton transfer reactions are involved. Furthermore, the a-carbanion/enamine intermediate (Ilia in Scheme 16.1) can be oxidized in enzymes containing a second cofactor, such as in the a-ketoacid dehydrogenases and pyruvate oxidases. In principal, this oxidation reaction corresponds to a hydride transfer reaction. 

One elegant way of in situ product removal is to use the product of a first dehydrogenase reaction as substrate for a subsequent enzymatic reaction, thus recycling the oxidized nicotinamide coenzyme (Fig. 16.2-3). Various NAD(P)-de-pendent enzymes can be applied as regeneration enzymes in this cascade reaction. 

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