Enzymatic reduction mechanism

As discussed earlier, Azo biological decolorization are mainly reduced in a direct reduction or mediated/indirect reduction with nonspecial azo reductase or reduced enzyme cofactors (Figs. 1 and 3). According to the direct enzymatic reduction mechanism, nonspecial azo reductase can catalyze the transfer of reducing equivalents originating from the oxidation of original electron donor in the azo dyes. In... 

Anaerobic bio-reduction of azo dye is a nonspecific and presumably extracellular process and comprises of three different mechanisms by researchers (Fig. 1), including the direct enzymatic reduction, indirect/mediated reduction, and chemical reduction. A direct enzymatic reaction or a mediated/indirect reaction is catalyzed by biologically regenerated enzyme cofactors or other electron carriers. Moreover, azo dye chemical reduction can result from purely chemical reactions with biogenic bulk reductants like sulfide. These azo dye reduction mechanisms have been shown to be greatly accelerated by the addition of many redox-mediating compounds, such as anthraquinone-sulfonate (AQS) and anthraquinone-disulfonate (AQDS) [13-15],... 

The acceleration mechanism of redox mediators are presumed by van der Zee [15]. Redox mediators as reductase or coenzymes catalyze reactions by lowering the activation energy of the total reaction. Redox mediators, for example, artificial redox mediators such as AQDS, can accelerate both direct enzymatic reduction and mediated/indirect biological azo dye reduction (Fig. 3). In the case of direct enzymatic azo dye reduction, the accelerating effect of redox mediator will be due to redox mediator enzymatic reduction in addition to enzymatic reduction of the azo dye. Possibly, both reactions will be catalyzed by the same nonspecific periplasmic enzymes. In the case of azo dye reduction by reduced enzyme cofactors, the accelerating effect of redox mediator will either be due to an electron shuttle between the reduced enzyme cofactor and redox mediator or be due to redox mediator enzymatic reduction in addition to enzymatic reduction of the coenzymes. In the latter case, the addition of redox mediator simply increases the pool of electron carriers. 

This mechanism is now considered to be of importance for the protection of LDL against oxidation stress, Chapter 25.) The antioxidant effect of ubiquinones on lipid peroxidation was first shown in 1980 [237]. In 1987 Solaini et al. [238] showed that the depletion of beef heart mitochondria from ubiquinone enhanced the iron adriamycin-initiated lipid peroxidation whereas the reincorporation of ubiquinone in mitochondria depressed lipid peroxidation. It was concluded that ubiquinone is able to protect mitochondria against the prooxidant effect of adriamycin. Inhibition of in vitro and in vivo liposomal, microsomal, and mitochondrial lipid peroxidation has also been shown in studies by Beyer [239] and Frei et al. [240]. Later on, it was suggested that ubihydroquinones inhibit lipid peroxidation only in cooperation with vitamin E [241]. However, simultaneous presence of ubihydroquinone and vitamin E apparently is not always necessary [242], although the synergistic interaction of these antioxidants may take place (see below). It has been shown that the enzymatic reduction of ubiquinones to ubihydroquinones is catalyzed by NADH-dependent plasma membrane reductase and NADPH-dependent cytosolic ubiquinone reductase [243,244]. 

Suresh Kumar G, Lipman R, Cummings J, et al. Mitomycin C-DNA adducts generated by DT-diaphorase. Revised mechanism of the enzymatic reductive activation of mitomycin C. Biochemistry 1997 36(46) 14128—14136. 

Azathioprine [a zah THIO preen] has been the cornerstone of immunosuppressive therapy over the last several decades. It has a nitroimidazoloyl side chain attached to the sulfur of 6-mercap-topurine, which is removed by non-enzymatic reduction in the body by glutathione to yield 6-mercaptopurine (6-MP). The latter is then converted to the corresponding nucleotide, thioinosinic acid (TIMP), by the salvage pathway enzyme, hypoxanthine-gua-nine phosphoribosyl transferase. The immunosuppressant effects of azathioprine are due to this fraudulent nucleotide. (See pp. 380-381 for a discussion of 6-MP s mechanism of action, resistance, pharmacokinetics, and adverse effects.) Because of their rapid proliferation in the immune response, and their dependence on de novo synthesis of purines required for cell division, lymphocytes are predominantly affected by the cytotoxic effects of azathioprine. The drug has little effect on suppressing a secondary immune response. 

Contents A. S. Mildvan, C. M. Grisham The Role of Divalent Cations in the Mechanism of Enzyme Catalyzed Phosphoryl and Nucleotidyl Transfer Reactions. - H.P.C.Hogenkamp, G.N.Sando The Enzymatic Reduction of Ribonucleotides. - W. T. Oosterhuis The Electronic State of Iron in Some Natural Iron Compounds. Determination by Mossbauer and ESR Spectroscopy. - A. Trautwein Mossbauer Spectroscopy on Heme Proteins. 

Biological degradation—fungi, bacteria, insects, termites Enzymatic reactions—oxidation, hydrolysis, reduction Chemical reactions—oxidation, hydrolysis, reduction Mechanical—chewing... 

In microbial iron assimilation, one mechanism for the release of iron from siderophores is the enzymatic reduction to the Fe state. Siderophore stability constants are much lower for Fe +, which has a lower charge-to-radius ratio. Moreover, ligand exchange reactions for the high-spin Fe ion are much faster than for the Fe ion. Stability constants of ferrous siderophores are experimentally difficult to obtain. Limiting pH-independent redox potentials can be utilized, however, to describe the electrochemical and chemical equilibria between fidly coordinated Fe + and Fe +-siderophore complexes and the uncomplexed Fe(H20)6 + and Fe(H20)e +, respectively, in a simple model as described in equation (5) ... 

One probable mechanism for the release of iron from siderophores to the agents which are directly involved in cell metabolism is enzymatic reduction to the ferrous state. Due to the very low affinity of hydrdxamate and catecholate siderophores for Fe(II), the reduction converts the tightly bound ferric ion to the ferrous complex, which is unstable with respect to protonation and dissociation at neutral pH or below. Therefore comparison of siderophore complex redox potentials with those of physiological reductants can be very useful for the clarification of the mechanism of iron metabolism. Table IV shows the redox potentials [obtained by cyclic voltammetry (see Fig. 18)) of the siderophores tested so far. The values of all of the hydroxamates are within the... 

The oxidation of diphenols to quinones is reversible, a variety of cellular reductants are able to mediate the reduction of quinones either by a two-electron mechanism or by two single-electron steps. The two-electron reduction can be catalyzed by carbonyl reductase and quinone reductase, while cytochrome P450 and some flavoproteins act by single-electron transfers. The non-enzymatic reduction of quinones can occur, for example, in the presence of O2 or some thiols such as GSH. 

Another possible mechanism of action of niridazole involves the inhibition of DNA synthesis in schistosomes, which is due to the presence of a 5-nitro function that undergoes enzymatic reduction to form reactive species. It has been suggested that the reactive species of niridazole may bind covalently to the parasite s macromolecules causing a decrease in nonprotein thiol content leading to death of the helminths [2,97,98]. 

In this section, we present the data on the enzymatic reactions of explosives relevant to the general cytotoxicity mechanisms of nitroaromatics (1) their single-electron enzymatic reduction to radicals accompanied by the formation of the reactive oxygen species (oxidative stress type of cytotoxicity) and (2) their two-electron reduction to nitroso and hydroxylamino metabolites causing the cytotoxicity by their covalent binding to proteins and DNA. 

Fig. 4. Mechanism and stereochemistry of enzymatic reduction of a 3-oxo-A -steroid to a 3-oxo-5 8-steroid (upper) and a 3-oxo-5a-steroid (lower section). Reprinted with permission from ref. 179.

T wo main classes of adenosylcobalamin-activated enzymes function by facilitating the homolytic scission of the Co-C5 to cob(II)alamin and the 5 -deoxyadenosyl radical. The resultant 5 -deoxyadenosyl radical initiates catalysis by abstraction of a hydrogen atom, either from a substrate in the case of the class of enzymes that catalyze radical isomerizations, or by abstraction of a hydrogen atom from Cys408-/3-SH in the active site of ribonucleotide reductase II. The resultant enzymatic thiyl radical initiates the reduction mechanism by abstraction of a hydrogen atom from the ribonucleotide substrate. We shall begin with the isomerization/elimination reactions of adenosylcobalamin. 

Purine deoxyribonucleotides are derived primarily from the respective ribonucleotide (Fig. 6.2). Intracellular concentrations of deoxyribonucleotides are very low compared to ribonucleotides usually about 1% that of ribonucleotides. Synthesis of deoxyribonucleotides is by enzymatic reduction of ribonucleotide-diphosphates by ribonucleotide reductase. One enzyme catalyzes the conversion of both purine and pyrimidine ribonucleotides and is subject to a complex control mechanism in which an excess of one deoxyribonucleotide compound inhibits the reduction of other ribonucleotides. Whereas the levels of the other enzymes involved with purine and pyrimidine metabolism remain relatively constant through the cell cycle, ribonucleotide reductase level changes with the cell cycle. The concentration of ribonucleotide reductase is very low in the cell except during S-phase when DNA is synthesized. While enzymatic pathways, such as kinases, exist for the salvage of pre-existing deoxyribosyl compounds, nearly all cells depend on the reduction of ribonucleotides for their deoxyribonucleotide... 

Brunmark and Cadenas (27A15) reviewed the major mechanisms that are involved in quinone-induced cytotoxicity in 1989. The redox chemistry of quinoid compounds was surveyed in terms of (1) reactions involving only electron transfers, such as those accomplished during the enzymatic reduction of quinones and nonenzymatic interaction with redox couples generating semiquinones, and (2) nucleophilic addition reactions. In their explanation of the mechanisms involved, quinone is reduced to the hydroquinone or semiqui-none radical by cellular reductase. The semiquinone radical then undergoes rapid autooxidation with the generation of the parent quinone and concomitant formation of superoxide. The hydroquinone reacts rapidly with superoxide to form H2O2 and the semiquinone. 

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