Oxidoreduction

Enzymatic oxidoreduction sequences lie at the heart of cellular energy metabolism. The energy released in oxidation of reduced organic or inorganic compounds is captured with varying efficiencies in useful forms such as ATP, membrane potentials, or reduced coenzymes. Because of their physiological role, the mechanism of action of enzymes catalyzing electron transfer processes has been actively studied. 

It should be recalled that redox enzymes or oxidoreductases are divided into four main classes. 

Nicotinamide adenine dinucleotide (NAD ) and nicotinamide adenine dinucleotide phosphate (NADP ) are pyridine nucleotides, first identified by O. Warburg in 1935. NAD is the coenzyme involved in dehydrogenase reactions and is reduced to NADH during the process. 

RPPRA = ribose-phosphate-phosphate-ribose-adenine 

The reaction is stereospecific and only one isomer (the a- or i -isomer in the above example) of NADH is produced. Other dehydrogenases with a different specificity are know to yield the j8-isomer stereospecifically rather than the a-isomer. 

The stereochemistry of the reduction was elucidated by use of [4A- H]NADPH, [4B- H]NADPH or the comparable forms of NADH only the tritium from the [4A- H]NADPH or [4A- H]NADH was incorporated into the product, probably in the 3 position [170]. Whether more than one 3-hydroxysteroid dehydrogenase active on 3-oxo-bile acids exists in cytosol of liver cells remains to be determined. 

Microsomal fractions contain 3a- and 3 -hydroxysteroid dehydrogenases which do not appear to be derived from cytosol [171]. Thus, microsomal 3a-hydroxysteroid dehydrogenase preferentially utilized [4B- H]NADH instead of [4A- H]NADPH preferred by the cytosolic enzyme. Microsomal 3)3-hydroxysteroid dehydrogenase was inactive toward ethanol, and thus is not an active component of alcohol dehydrogenase [172]. These dehydrogenases were active with ,9, C21, C24 and C27 

3-oxosteroids, and showed a higher ratio of 3a/3 products from C,- and C2,-steroids with microsomal preparations from female rats than from male rats regardless of the configuration at C-5. Only 3-oxo-5/8-cholanate was studied in these experiments, where the rate of product formation and ratio of epimers (3a/3j8) was greater with NADH -I- microsomes from females, whereas the rate was greater with NADPH + microsomes from males [171]. 

A study of the reduction of [24- C]3-oxo-5j8-cholanic acid in bile fistula rats given [l- Hjjethanol showed that all metabolites had a 3a-hydroxy group and all radioactive products (lithocholate, 3a,6/8-dihydroxy-5 -cholanate, chenodeoxycho-late and y8-muricholate) contained about 13 atom% excess deuterium in the 3/9 position. Thus, the 3)8-hydroxy-5/9-steroid dehydrogenase isoenzyme of alcohol dehydrogenase [172] has no function in the reductive metabolism of bile acids. Cholic acid was not radioactive but contained deuterium at the 3)8, 5)8 and other positions, probably because of the transfer of deuterium from ethanol via NADH to NADPH, which it utilized in the biosynthesis of cholesterol and bile acids and in oxido reduction of the 3-hydroxyl group of the latter [173]. 

Although cholesterol is the major source of 5)9-bile acids, an unsaturated acid, 3)8-hydroxy-5-cholenic acid [174] has been found in meconium, mainly as the sulfate [175], in bile of a boy with a deficiency of 3)8-hydroxysteroid dehydrogenase [176], and in urine of healthy persons and individuals with liver disease [164]. The details of metabolism of 3)8-hydroxy-5-cholenic acid to lithocholate have not been entirely elucidated, but the mechanism for conversion of the 3/8-hydroxy-A to the 3-oxo-A derivative has been formulated in the C27 series (cf. Chapter 9). Briefly, the 3)8-ol is dehydrogenated by a microsomal enzyme fortified with NAD to provide the 3-oxo-A system [177,178]. Whether a A - A isomerase is essential is not known, since there is no direct evidence for the formation of the intermediary 3-oxo-A system the rate-limiting step is the dehydrogenation of the 3)8-ol which may prevent accumulation of the 3-oxo-A system [177]. The reduction of the double bond at 4-5 to the 5)8- or 5a-bile acid is catalyzed by the respective A -3-oxosteroid 5)8- or 5 -reductase obtained from liver cytosol [170], and has been purified about 10-fold [178]. The formation of the 3-oxo-5/9 derivative requires the enzyme and NADPH the proton from the A side (4A-NADPH) appeared in the product as the 5)8-H, whereas the proton at C-4 is derived from the aqueous medium. Formation of the 5a derivative requires (4B-NADPH) in a similar mechanism (Fig. 4) [179], Reduction of the 3-0X0 product is then catalyzed by 3a-hydroxysteroid dehydrogenase as discussed above. 

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Sensitizers as well as desensitizers form a reversal oxidoreduction system with silver halides, according to both pH and pAg of the photographic emulsion. But besides the specific influence of the emulsion, the efficiency of a sensitizing dye depends on many other factors such as its adsorption, its spectral absorption, the energetic transfer yield, the dye aggregate to the silver halide, and finally on its desensitizing property in... 

Ortho esters, in synthesis of symmetrical trimethine thiazolocyanines, 54 Oxazolone, for neutrocyanines, 27 Oxidation potentials, of dyes, 75 of mesosubstituted dyes, in relation with absorption, 77 of polymethine dyes, 72 Oxidoreduction, relation between sensitizers, and silver halides, 78 4-Oxo-disubstituted 2-aminoselenazoles, table of products, 262 Oxonols, nomenclature of, 26 in synthesis of dimethine neutrocyanines, 62... 

Figure 11-2. Oxidoreduction of isoalloxazine ring in fiavin nucieotides via a semi-quinone (free radicai) intermediate (center).

An additional component is the iron-sulfur protein (FeS nonheme iron) (Figure 12-6). It is associated with the flavoproteins (metallofiavoproteins) and with cytochrome b. The sulfur and iron are thought to take part in the oxidoreduction mechanism between flavin and Q, which involves only a single e change, the iron atom undergoing oxidoreduction between Fe " and Fe k... 

Flavin Coenzymes Are Electron Carriers in Oxidoreduction Reactions... 

GSHPx, CAT and SOD, which normally protect cells from free-radical damage have not been detected in aqueous humour. It has therefore been su ested that damage by free radicals and hydrogen peroxide to the anterior segment is prevented by a non-enzymatic extracellular oxidoreduction system involving a constant supply of reduced glutathione to the aqueous fluid from the ciliary epithelium, cornea and lens (Riley, 1983). 

Husain, M. and Husain, Q. (2008) Applications of redox mediators in the treatment of organic pollutants by using oxidoreductive enzymes a review. Critical Reviews in Environmental Science and Technology, 38, 1-42. 

Proteinoids also have other properties, such as the formation of cell-like structures (microspheres), and they show weak or very weak activities such as decarboxylation (Rohlfing, 1967) or oxidoreduction (Dose and Zaki, 1971). 

Dec J, Bollag JM (1990) Detoxification of substituted phenols by oxidoreductive enzymes through polymerization reactions. Arch Environ Contam Toxicol 19 543-550... 

Husain Q (2006) Potential applications of the oxidoreductive enzymes in the decolorization and detoxification of textile and other synthetic dyes from polluted water a review. Crit Rev Biotechnol 26 201-221... 

Oxidoreduction driven Methyl transfer driven Light absorption driven... 

Hoch U, ScheUer G, Schmitt M, Schreier P, Adam W, Saha-MoUer CR (1995) Enzymes in synthetic organic chemistry selective oxidoreductions catalyzed by the metaUoenzymes lipoxygenase and peroxidase. In Werner H, Simdermeyer J (eds) Stereoselective reactions of metal-activated molecules, 2nd Symposium. Vieweg, Braimschweig, p 33 Adam W, Korb MN (1997) Tetrahedron Asymmetry 8 1131... 

Hydrogenase Otho H2o para H2 conversion, cytochrome c3 oxidoreduction Yagi et al., 1969 [1] Kimura et al.,1979 [2]... 

Lactate and pyruvate are interconverted within the cytoplasm, depending upon the NADiNADH ratio. In the cytoplasm, the ratio of lactate to pyruvate reflects the oxidoreduction state. 

The synthesis of adrenal steroids is illustrated in Fig. 5.3.1. Cortisol, corticosterone, and aldosterone are formed by sequential hydroxylations and oxidoreductions from pregnenolone and progesterone. 17a-Hydroxypregnenolone (17HP) is a branchpoint constituent because it can be converted to cortisol or adrenal androgens. All of the components of this pathway can be quantified by MS/MS. The steroids around the periphery are urinary metabolites and these are measured by GC-MS following hydrolysis of conjugates and derivatization. 

While defective 11/1HSD I seemed the most likely cause of the disorder, no loss-of-function mutations were found in 1 IjSHSD I in the first patients investigated [61 ]. The cause of the disorder in these cases proved to be mutations in hexose-6-phos-phate dehydrogenase (H6PDH), the enzyme that supplies electrons to the NADPH utilized in oxidoreduction [15]. Later studies have found 11/311814 I mutations in some affected individuals. Thus, there are two monogenic disorders giving rise to a similar phenotype cortisone reductase deficiency caused by lljSHSD I mutations,... 

In the case of two flavoenzyme oxidase systems (glucose oxidase (18) and thiamine oxidase s where both oxidation-reduction potential and semiquinone quantitation values are available, semiquinone formation is viewed to be kinetically rather than thermodynamically stabilized. The respective one-electron redox couples (PFl/PFl- and PFI7PFIH2) are similar in value (from essential equality to a 50 mV differential) which would predict only very low levels of semiquinone (32% when both couples are identical) at equilibrium. However, near quantitative yields (90%) of semiquinone are observed either by photochemical reduction or by titration with dithionite which demonstrates a kinetic barrier for the reduction of the semiquinone to the hydroquinone form. The addition of a low potential one-electron oxidoreductant such as methyl viologen generally acts to circumvent this kinetic barrier and facilitate the rapid reduction of the semiquinone to the hydroquinone form. 

Although far from exhaustive, Table 3 shows that tetracoordinated compounds as diverse as phosphonium salts, phosphinates, thiophosphinates, phosphine oxides, phos-phonium ylides and halophosphates can ail lead to P(V) derivatives by addition, substitution, or oxidoreduction reactions. 

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