Redox reactions pyruvate

The reasons for the confusion surrounding the mechanism of the malo-lactic fermentation are now apparent. In the malate system from Lactobaccillus plantarum, Korkes et al. (14) demonstrated carbon dioxide and lactic acid production from malic acid, but they were unable to show a large amount of pyruvic acid production. However, the cofactor requirement for the system indicated the need for an intermediate between malic acid and lactic acid, and pyruvic acid was the logical choice. At this time, the occurrence of enzymes requiring NAD in a function other than reduction-oxidation was not realized, so it was logical to conclude that the malic acid to lactic acid conversion involved a redox reaction. The later information, however, indicates that this is probably not the case. 

It is important not to confuse the reactions of Eq. 17-42 as they occur in an aerobic cell with the tightly coupled pair of redox reactions in the homolactate fermentation (Fig. 10-3 Eq. 17-19). Tire reactions of steps a and c of Eq. 17-42 are essentially at equilibrium, but the reaction of step b may be relatively slow. Furthermore, pyruvate is utilized in many other metabolic pathways and ATP is hydrolyzed and converted to ADP through innumerable processes taking place within the cell. Reduced NAD does not cycle between the two enzymes in a stoichiometric way and the "reducing equivalents" of NADH formed are, in large measure, transferred to the mitochondria. The proper view of the reactions of Eq. 17-42 is that the redox pairs represent a kind of redox buffer system that poises the NAD+/NADH couple at a ratio appropriate for its metabolic function. 

A number of enzymes contain other carbonyl compounds that catalyze reactions in the same way as does pyridoxal phosphate or that catalyze redox reactions. Such compounds include pyruvate (Section 9.8.1) pyrroloquino-line quinone, which may be a dietary essential (Section 9.8.2) and a variety... 

Figure 11.8 Mechanism of redox reaction catalyzed by NAD dependent lactate dehydrogenase Lactate dehydrogenase (EC 1.1.1.27) is a tetrameric enzyme which catalyzes the reversible redox reaction between L-lactate and pyruvate via ordered kinetic sequence. The hydride ion is transferred to the proR side of the 4 position of NAD. His 195 acts as an acid-base catalyst removing the proton from lactate during oxidation. The active site loop (residues 98-110) carries Argl09 which helps stabilize the transition state during hydride transfer and contacts required for the substrate specificity.

Redox reactions are essential for life. For example, the enzyme-catalyzed reduction of pyruvate to lactate is a step in the anaerobic fermentation of sugar by bacteria ... 

Fig. 2 Electron-transfer pathway in dehydrogenase-catalyzed reactions coupled to electrodes via electrochemical redox reactions of the coenzymes. Electron fluxes represent the oxidation of the substrate (e.g. Pyruvate/Lactate ° = -435 mV vs. SCE, pH 7.0).

Redox reactions Another way to resolve racemic mixtures is the enzyme-catalyzed oxidative transformation of the undesired enantiomer. This approach was used for the synthesis of (5)-[3-"C]valine (14). For this purpose chemically synthesized racemic [3-"C]valine was treated with immobilized (/ )-amino acid oxidase (EC 1.4.3.3). This converted the undesired (7 )-enantiomer to [3-"C]pyruvic acid (15), which could be easily removed by HPLC. (5)-[3-"C]Valine was obtained in e.e.s of 90-99%, even though reaction times were held to 17 min or less because of the 20 minute half-life of carbon-11. 

Most coenzymes have aromatic heterocycles as major constituents. While enzymes possess purely protein structures, coenzymes incorporate non-amino acid moieties, most of them aromatic nitrogen het-erocycles. Coenzymes are essential for the redox biochemical transformations, e.g., nicotinamide adenine dinucleotide (NAD, 13) and flavin adenine dinucleotide (FAD, 14) (Scheme 5). Both are hydrogen transporters through their tautomeric forms that allow hydrogen uptake at the termini of the quinon-oid chain. Thiamine pyrophosphate (15) is a coenzyme that assists the decarboxylation of pyruvic acid, a very important biologic reaction (Scheme 6). 

TPP-dependent enzymes catalyze either simple decarboxylation of a-keto acids to yield aldehydes (i.e. replacement of C02 with H+), or oxidative decarboxylation to yield acids or thioesters. The latter type of reaction requires a redox coenzyme as well (see below). The best known example of the former non-oxidative type of decarboxylation is the pyruvate decarboxylase-mediated conversion of pyruvate to acetaldehyde and C02. The accepted pathway for this reaction is shown in Scheme 10 (69MI11002, B-70MI11003, B-77MI11001>. 

Some examples follow that illustrate the remarkable specificity of this kind of redox system. One of the last steps in the metabolic breakdown of glucose (glycolysis Section 20-10A) is the reduction of 2-oxopropanoic (pyruvic) acid to L-2-hydroxypropanoic (lactic) acid. The reverse process is oxidation of l-lactic acid. The enzyme lactic acid dehydrogenase catalyses this reaction, and it functions only with the L-enantiomer of lactic acid ... 

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