Reductive enzymes

The requirement for reduction prior to DNA alkylation and crosslinking was first demonstrated by Iyer and Szybalski in 1964 [29], and can be induced both by chemical reducing agents such as sodium dithionite and thiols in vitro and by various reductive enzymes such as DT-diaphorase (NAD(P)H-quinone oxidoreduc-tase) in vitro and in vivo [47]. Much work to characterize the mechanism of reductive activation and alkylation has been carried out, principally by the Tomasz and Kohn groups, and Figure 11.1 illustrates a generally accepted pathway for mitomycin C [16, 48-50] based on these experiments, which is very similar to the mechanism originally proposed by Iyer and Szybalski [29]. 

BUDDINGTON R K, WILLIAMS 0 H, CHEN s-c, wiTHERLY, s T (1996) Dietary Supplement of neosuger alters the fecal flora and decreases activities of some reductive enzymes in human subjects. J Clin Nutr. 63 709-16. 

Cummings, J. The role of reductive enzymes in cancer cell resistance to mitomycin C. Drug Resist. Update 2000, 3, 143-148. 

There are also voices critical of the rTCA cycle Davis S. Ross has studied kinetic and thermodynamic data and concludes that the reductive, enzyme-free Krebs cycle (in this case the sequence acetate-pyruvate-oxalacetate-malate) was not suitable as an important, basic reaction in the life evolution process. Data on the Pt-catalysed reduction of carbonyl groups by phosphinate show that the rate of the reaction from pyruvate to malate is much too low to be of importance for the rTCA cycle. In addition, the energy barrier for the formation of pyruvate from acetate is much too high (Ross, 2007). 

By analogy with the biosynthesis of L-ascorbic acid and with other oxidation-reduction enzyme systems, it seems likely that D-galactose is oxidized to D-galacturonic acid (XXIII) on reduction at Cl, this yields L-galactonic acid (XXIV), the 1,5-lactone (XXV) of which, on reduction at Cl, would give L-galactose (XXII). 

Chapter 10 covers reductive enzymes with an emphasis on transaminase enzymes, which are enjoying widespread application in the synthesis of nonnatural amino acids which are key building blocks for several products of industrial importance. 

Frazao C, Silva G, Gomes CM, et al. 2000. Structure of a dioxygen reduction enzyme from Desulfovibrio gigas. Nat Struct Biol 7 1041-5. 

Redox reaetions and hydrolysis are the predominant metabolie eonversions triggered by the intestinal microflora. The main reductive enzymes produeed by the intestinal mieroflora are nitroreductase, deaminase, urea dehydroxylase, and azoreduetase the hydrolytic enzymes are P-glucoronidase, P-xylosidase, P-galaetosidase, and a-L-arabinosidase. Studies conducted by Macfarlane and co-workers have shown that proteolysis ean also happen in the colon [31]. More recent findings by this group indieate that bacterial fermentation of proteins in humans could account for 17% of... 

ISOTOPE EXCHANGE AT EQUILIBRIUM WEDLER-BOYER TECHNIQUE CUMULATIVE INHIBITION UNCONSUMED SUBSTRATE CRYPTIC CATALYSIS BOROHYDRIDE REDUCTION ENZYME CASCADE KINETICS... 

HA can be produced by catalytic oxidation of ammonia with hydrogen peroxide or by catalytic reduction of nitrates with hydrogen . Analogously, oxidative and reductive enzymic pathways in which HA is produced from either ammonia or nitrate have been identified in a variety of biological systems. 

As with adults, the primary organ responsible for drug metabolism in children is the liver. Although the cytochrome P450 system is fully developed at birth, it functions more slowly than in adults. Phase I oxidation reactions and demethylation enzyme systems are significantly reduced at birth. However, the reductive enzyme systems approach adult levels and the methylation pathways are enhanced at birth. This often contributes to the production of different metabolites in newborns from those in adults. For example, newborns metabolize approximately 30% of theophylline to caffeine rather than to uric acid derivatives, as occurs in adults. While most phase I enzymes have reached adult levels by 6 months of age, alcohol dehydrogenase activity appears around 2 months of age and approaches adult levels only by age 5 years. 

Makinen, M. W., Schichman, S. A., Hill, S. C., and Gray, H. B. (1983). Heme-heme orientation and electron transfer kinetic behavior of multisite oxidation-reduction enzymes. Science 222, 929-931. 

The first examples of mechanism must be divided into two principal classes the chemistry of enzymes that require coenzymes, and that of enzymes without cofactors. The first class includes the enzymes of amino-acid metabolism that use pyridoxal phosphate, the oxidation-reduction enzymes that require nicotinamide adenine dinucleotides for activity, and enzymes that require thiamin or biotin. The second class includes the serine esterases and peptidases, some enzymes of sugar metabolism, enzymes that function by way of enamines as intermediates, and ribonuclease. An understanding of the mechanisms for all of these was well underway, although not completed, before 1963. 

Palmer, G., Mildvan, A. S. in Structure and Function of Oxidation-Reduction Enzymes. Akeson, A., Ehrenberg, A. (eds.), p. 385. Oxford Pergamon Press 1972... 

These are involved in a wide range of electron-transfer processes and in certain oxidation-reduction enzymes, whose function is central to such important processes as the nitrogen cycle, photosynthesis, electron transfer in mitochondria and carbon dioxide fixation. The iron-sulfur proteins display a wide range of redox potentials, from +350 mV in photosynthetic bacteria to —600 mV in chloroplasts. 

The cell metabolism is based on the oxidation-reduction enzyme activity. These enzymes are called oxidoreductases and divided into the following groups ... 

Oxidoreductases comprise a large class of enzymes that catalyze biological oxidation/reduction reactions. Because so many chemical transformation processes involve oxidation/reduction processes, the idea of developing practical applications of oxidoreductase enzymes has been a very attractive, but quite elusive, goal for many years [83], Applications have been sought for the production of pharmaceuticals, synthesis and modification of polymers, and the development of biosensors for a variety of clinical and analytical applications [83], In recent years, the use of oxido-reductive enzymes to catalyze the removal of aromatic compounds from... 

Structure and Function of Oxidation Reduction Enzymes, A. Akeson and A. Ehrenberg, Eds., pp. 541-547, Pergamon, Oxford, 1972. 

A3. Agner, K., Biological effects of hypochlorous acid formed by MPO peroxidation in the presence of cloride ions. In Structure andFunction of Oxidation-Reduction Enzymes, pp. 329— 335. Pergamon Press, Oxford, UK, 1972. 

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