Enzymes reductase

Major reduction reactions are azo reduction and nitro reduction. The enzymes (reductases) are found in gut flora but also mammalian tissues. Reduction catalyzed by cytochrome P-450 can occur (e.g., dehalogenation). DT diaphorase carries out two-electron reductions. 

The activities involved in yeast fatty acid biosynthesis are covalently linked as separate domains of two multifunctional polypeptides, a and p, encoded by the fas2 and fasl genes, respectively (Fig. 2) [57,58]. The functionalities associated with the 220 kDa a subunit include -ketoacyl synthase activity, -ketoacyl reductase activity, and an AGP domain which bears a phosphopantetheinylated serine. The 208 kDa -subunit has acetyl and malonyl CoA transacylase, palmi-toyl transferase, -hydroxyacyl-enzyme dehydratase, and enoyl acyl-enzyme reductase activities. The two subunits can be readily dissociated, and the individual activities maybe measured [57]. 

The enzymic reduction of geraniol and nerol to citronellol was mentioned in Vol. 1, p. 8 Dunphy and Allcock have now isolated a solubilized enzyme reductase from rose petals that is specific for the reduction of primary terpene alcohols with either a cis- or a trans-aWylk double bond. A pseudomonade has been found that converts linalool into camphor and 2,6-dimethyl-6-hydroxyocta-2,7-dienoic acid. ... 

While hemoglobin can exist in both the Fe(II) and Fe(III) state, it normally functions as an oxygen carrier in the Fe(II) state. However, each day about 1-2% of the hemoglobin is autooxidized to methemoglobin (Fe(III)) but in the red blood cell there are enzymes (reductases) which convert the oxidized hemoglobin to the Fe(II) state . ... 

The chanoclavine cyclase activity is dependent on NADH or NADPH, Mg, and ATP (10). The scheme we propose here is consistent with an NAD(P)H requirement for the third enzyme (reductase). Also, we expect the oxidized form, NADP or NAD, to oxidize 16 to aldehyde 17. Furthermore, and as stated above, it is possible that NAD(P)H is involved in the oxidation and reduction reactions to generate iminium ion 21. However, it is not obvious why there is a requirement for ATP. Clearly, elucidation of the mechanisms underlying the steps in D-ring formation will continue to reveal some interesting biochemistry. 

Figure 5.1 (a) Mediated Mo enzyme (reductase) electrochemistry and (b) direct Mo... 

Willstatter s work on enzymes continued that of Emil Fischer (see p. 827). He used methods of adsorption and elution to obtain purer forms, which were increasingly unstable. He concluded that they consist of colloidal material combined with a chemically active group, but later research indicates that they are really individual proteins. The discovery of a number of enzymes has been mentioned in earlier chapters. The enzyme reductase in yeast was recognised and called philothion by J. de Rey-Pailhade. He found that if yeast is... 

The reduction of racemic 5 is a nice example of product-selective biocatalytic kinetic resolution. This means that the enantiomer that is reduced affords only one of two possible diastereomers. Enzyme reductase from the cells of Saccharomyces cerevisiae (baker s yeast) selectively reduces the carbonyl group in the S-enantiomer of 5 into alcohol with an S configuration on the new stereogenic center, hence producing (IS, 2S)-6. Due to the C-H acidify of the a-C atom in 5, it easily tautomerizes to enols 5a and 5b in equilibrium (Scheme 5.36). 

Oxidoreduciases. Enzymes catalysing redox reactions. The substrate which is oxidized is regarded as the hydrogen donor. This group includes the trivially named enzymes, dehydrogenases, oxidases, reductases, peroxidases, hydrogenases and hydroxylases. 

A substantial fraction of the named enzymes are oxido-reductases, responsible for shuttling electrons along metabolic pathways that reduce carbon dioxide to sugar (in the case of plants), or reduce oxygen to water (in the case of mammals). The oxido-reductases that drive these processes involve a small set of redox active cofactors , that is, small chemical groups that gain or lose electrons. These cofactors include iron porjDhyrins, iron-sulfur clusters and copper complexes as well as organic species that are ET active. 

Fig. 7.15 The variation in torsion angles can be effectively represented as a series of dials, where the time corresponds to the distance from the centre of the dial. Data from a molecular dynamics simulation of an intermolecular complex between the enzyme dihydrofolate reductase and a triazine inhibitor [Leach and Klein 1995].

He/minthosporium (15). The mode of action is considered to be inhibition of the enzyme NADPH-cytochrome C reductase, which results in the generation of free radicals and/or peroxide derivatives of flavin which oxidize adjacent unsaturated fatty acids to dismpt membrane integrity (16) (see Enzyme inhibitors). 

Biosynthesis of Tea Flavonoids. The pathways for the de novo biosynthesis of flavonoids in both soft and woody plants (Pigs. 3 and 4) have been generally elucidated and reviewed in detail (32,51). The regulation and control of these pathways in tea and the nature of the enzymes involved in synthesis in tea have not been studied exhaustively. The key enzymes thought to be involved in the biosynthesis of tea flavonoids are 5-dehydroshikimate reductase (52), phenylalanine ammonia lyase (53), and those associated with the shikimate/arogenate pathway (52). At least 13 enzymes catalyze the formation of plant flavonoids (Table 4). 

Diacetyl, acetoin, and diketones form during fermentation. Diacetyl has a pronounced effect on flavor, with a threshold of perception of 0.1—0.2 ppm at 0.45 ppm it produces a cheesy flavor. U.S. lager beer has a very mild flavor and generally has lower concentrations of diacetyl than ale. Diacetyl probably forms from the decarboxylation of a-ethyl acetolactate to acetoin and consequent oxidation of acetoin to diacetyl. The yeast enzyme diacetyl reductase can kreversibly reduce diacetyl to acetoin. Aldehyde concentrations are usually 10—20 ppm. Thek effects on flavor must be minor, since the perception threshold is about 25 ppm. 

The second type of antifolates bind preferentially with, and thus selectively inhibit, the enzyme dihydrofolate reductase contained in the plasmodia. This interferes with the abiUty of the malaria parasites to convert dihydrofolate to tetrahydrofoUc acid. In the erythrocyte host, however, dihydrofolate... 

An important dmg in the regulation of cholesterol metaboHsm is lovastatin [75330-75-5] which is an HMG—CoA reductase inhibitor (see Cardiovascularagents). p-Hydroxy-p-methyl glutarate—coenzyme A (HMG—CoA) reductase is the rate-limiting enzyme of cholesterol synthesis. Lovastatin is actually a prodmg, which is eventually hydrolyzed in the Hver to its active, P-hydroxylated form (5). 

The most conspicuous use of iron in biological systems is in our blood, where the erythrocytes are filled with the oxygen-binding protein hemoglobin. The red color of blood is due to the iron atom bound to the heme group in hemoglobin. Similar heme-bound iron atoms are present in a number of proteins involved in electron-transfer reactions, notably cytochromes. A chemically more sophisticated use of iron is found in an enzyme, ribo nucleotide reductase, that catalyzes the conversion of ribonucleotides to deoxyribonucleotides, an important step in the synthesis of the building blocks of DNA. 

Figure 1.9 Examples of functionally important intrinsic metal atoms in proteins, (a) The di-iron center of the enzyme ribonucleotide reductase. Two iron atoms form a redox center that produces a free radical in a nearby tyrosine side chain. The iron atoms are bridged by a glutamic acid residue and a negatively charged oxygen atom called a p-oxo bridge. The coordination of the iron atoms is completed by histidine, aspartic acid, and glutamic acid side chains as well as water molecules, (b) The catalytically active zinc atom in the enzyme alcohol dehydrogenase. The zinc atom is coordinated to the protein by one histidine and two cysteine side chains. During catalysis zinc binds an alcohol molecule in a suitable position for hydride transfer to the coenzyme moiety, a nicotinamide, [(a) Adapted from P. Nordlund et al., Nature 345 593-598, 1990.)...

The statins lower cholesterol by inhibiting the enzyme 3-hydroxy-3-methylglutaryl coenzyme A reductase, which is required for the biosynthesis of mevalonic acid (see Section 26.10). Mevalonic acid is an obligatory precursor to cholesterol, so less mevalonic acid translates into less cholesterol. 

A portion of the DNA sequence of nit-6, the Neurospora gene encoding the enzyme nitrite reductase. (JaviesD. Cotandene, University of Virginia ... 

As its name implies, this complex transfers a pair of electrons from NADH to coenzyme Q a small, hydrophobic, yellow compound. Another common name for this enzyme complex is NADH dehydrogenase. The complex (with an estimated mass of 850 kD) involves more than 30 polypeptide chains, one molecule of flavin mononucleotide (FMN), and as many as seven Fe-S clusters, together containing a total of 20 to 26 iron atoms (Table 21.2). By virtue of its dependence on FMN, NADH-UQ reductase is a jlavoprotein. 

Although the precise mechanism of the NADH-UQ reductase is not known, the first step involves binding of NADH to the enzyme on the matrix side of the inner mitochondrial membrane, and transfer of electrons from NADH to tightly bound FMN ... 

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