Reduction by enzymes

At the same time ubiquinone Qio itself is the subject of reduction by enzyme NAD(P)H-dependent quinone oxidoreductase (DT-diaphorase) [17] ... 

Gillette, J.R. (1966) Biochemistry of drug oxidation and reduction by enzymes in hepatic endoplasmic reticulum. Advances in Pharmacology, 4, 219-261. 

Gillette, J. R., Biochemistry of Drug Oxidation and Reduction by Enzymes in Hepatic Endoplasmic Reticulum, in Advances in Pharmacology, Vol. 4 (Garattini, S. and Shore, P. A., Eds.). Academic Press, New York, 1966, p. 219. 

Many biological processes involve oxidation of alcohols to carbonyl compounds or the reverse process reduction of carbonyl compounds to alcohols Ethanol for example is metabolized m the liver to acetaldehyde Such processes are catalyzed by enzymes the enzyme that catalyzes the oxidation of ethanol is called alcohol dehydrogenase... 

FIGURE 21.V The fatty acyl-CoA dehydrogenase reaction, emphasizing that the reaction involves reduction of enzyme-bonnd FAD (indicated by brackets). 

Consonant with the present interest in chiral synthesis, two additional contributions can be cited. Sih al utilized a combined microbiological and organic chemical sequence in which key chirality establishing steps include the conversion of to chiral, but unstable, 18 by enzymic reduction using the fungus Diplodascus uninucleatus. Lower side-chain synthon was prepared by reduction of achiral with Pencillium decumbens. 

This lactamization process can be promoted by enzymes such as pancreatic porcine lipase. Reduction of co-azido carboxylic acids leads to macrocyclic lactams. Although treatment of carboxylic acids with amines does not directly give amides, the reaction can be made to proceed in good yield at room temperature or... 

It is probable that the negative charge induced by these three electrons on FeMoco is compensated by protonation to form metal hydrides. In model hydride complexes two hydride ions can readily form an 17-bonded H2 molecule that becomes labilized on addition of the third proton and can then dissociate, leaving a site at which N2 can bind (104). This biomimetic chemistry satisfyingly rationalizes the observed obligatory evolution of one H2 molecule for every N2 molecule reduced by the enzyme, and also the observation that H2 is a competitive inhibitor of N2 reduction by the enzyme. The bound N2 molecule could then be further reduced by a further series of electron and proton additions as shown in Fig. 9. The chemistry of such transformations has been extensively studied with model complexes (15, 105). 

For bio-transformation processes, immobilised enzymes are often used because their activity persists over a longer period of time than that of free enzymes. The reduction of enzyme activity in enzymatic reactors is a consequence of energy dissipation by sparging and stirring, which is required for instance for oxygen transport or realisation of constant reaction conditions as regards temperature and pH. In the other hand low and high pH-values leads also to a decrease of enzyme activity and increase the stress sensitivity. 

One way in which to determine whether one part of the molecule may influence the structure about the N-terminus, or whether the assignments of the [ C]methyl resonances in the C-n.m.r. spectra of fully reductively [ CJmethylated glycophorins A and A are correct is to isolate the various glycophorin glycopeptides that have been produced by enzymic or chemical means. 

The degradation of trichloroethene by methylotrophic bacteria involves the epoxide as intermediate (Little et al. 1988). Further transformation of this may produce CO that can toxify the bacterium, both by competition for reductant and by enzyme inhibition (Henry and Grbic-Galic 1991). The inhibitory effect of CO may, however, be effectively overcome by adding a reductant such as formate. 

Electrochemical processes are particularly well suited for the manufacture of fine chemicals in view of their high sjjecificity (almost comparable to that offered by enzymes), the smaller number of steps required, adoption of milder conditions, lack of scale-up problems, avoidance of effluents, etc. The ease with which oxidation and/or reduction can be carried out with the practically mass-free clean electrons makes electrochemical processes well suited for such jobs, including paired synthesis in effect, we use electricity as a reagent . Consider a standard chemical oxidant like manganic or chromic sulphate. Here, a stoichiometric amount of the reduced salt will be formed the disposal of which can be a serious problem. If we adopt an electrochemical process, then the reduced salt is converted into the desired oxidized salt. 

Reduction by available peroxidase enzymes, e.g. glutathione peroxidase ... 

Figure 17.6 Redox hydrogel approach to immobilizing multiple layers of a redox enzyme on an electrode, (a) Structure of the polymer, (b) Voltammograms for electrocatalytic O2 reduction by a carbon fiber electrode modified with laccase in the redox hydrogel shown in (a) (long tether) or a version with no spacer atoms in the tether between the backbone and the Os center (short tether). Reprinted with permission fi om Soukharev et al., 2004. Copyright (2004) American Chemical Society.

Figure 17.7 Electrocatalysis of O2 reduction by Pycnoporus cinnabarinus laccase on a 2-aminoanthracene-modified pyrolytic graphite edge (PGE) electrode and an unmodified PGE electrode at 25 °C in sodium citrate buffer (200 mM, pH 4). Red curves were recorded immediately after spotting laccase solution onto the electrode, while black curves were recorded after exchanging the electrochemical cell solution for enzyme-fiiee buffer solution. Insets show the long-term percentage change in limiting current (at 0.44 V vs. SHE) for electrocatalytic O2 reduction by laccase on an unmodified PGE electrode ( ) or a 2-aminoanthracene modified electrode ( ) after storage at 4 °C, and a cartoon representation of the probable route for electron transfer through the anthracene (shown in blue) to the blue Cu center of laccase. Reproduced by permission of The Royal Society of Chemistry fi om Blanford et al., 2007. (See color insert.)...

The alcohol tolerance of O2 reduction by bilirubin oxidase means that membraneless designs should be possible provided that the enzymes and mediators (if required) are immoblized at the electrodes. Minteer and co-workers have made use of NAD -dependent alcohol dehydrogenase enzymes trapped within a tetraaUcylammonium ion-exchanged Nafion film incorporating NAD+/NADH for oxidation of methanol or ethanol [Akers et al., 2005 Topcagic and Minteer, 2006]. The polymer is coated onto an electrode modified with polymethylene green, which acts as an electrocatalyst... 

Zhu, D., Yang, Y., Buynak, J.D. and Hua, L. (2006) Stereoselective ketone reduction by a carbonyl reductase from Sporobolomyces salmonicolor. Substrate specificity, enantioselectivity and enzyme—substrate docking studies. Organic and Biomolecular Chemistry, 4 (14), 2690-2695. 

---