Nicotinamide adenine dinucleotide biological oxidations with

Newman, Melvin S., 93 Newman projection, 93 molecular model of, 93 Nicotinamide adenine dinucleotide, biological oxidations with, 625-626 reactions of, 725 structure of, 725, 1044 Nicotinamide adenine dinucleotide (reduced), biological reductions with, 610-611... 

Alcohol dehydrogenases (ADH EC 1.1.1.1), for which several X-ray structures are available ", catalyze the biological oxidation of primary and secondary alcohols via the formal transfer of a hydride anion to the oxidized form of nicotinamide adenine dinucleotide (NAD ), coupled with the release of a proton. Liver alcohol dehydrogenase (LADH) consists of two similar subunits, each of which contains two zinc sites, but only one site within each subunit is catalytically active. The catalytic zinc is coordinated in a distorted tetrahedral manner to a histidine residue, two cysteine residues and a water molecule. The remaining zinc is coordinated tetrahedrally to four cysteine residues and plays only a structural role . 

Reduced nicotinamide-adenine dinucleotide (NADH) plays a vital role in the reduction of oxygen in the respiratory chain [139]. The biological activity of NADH and oxidized nicotinamideadenine dinucleotide (NAD ) is based on the ability of the nicotinamide group to undergo reversible oxidation-reduction reactions, where a hydride equivalent transfers between a pyridine nucleus in the coenzymes and a substrate (Scheme 29a). The prototype of the reaction is formulated by a simple process where a hydride equivalent transfers from an allylic position to an unsaturated bond (Scheme 29b). No bonds form between the n bonds where electrons delocalize or where the frontier orbitals localize. The simplified formula can be compared with the ene reaction of propene (Scheme 29c), where a bond forms between the n bonds. 

NAD is one of Nature s most important oxidizing agents it can be considered as a biological equivalent of the chromium(VI) ion. NAD is shorthand for nicotinamide adenine dinucleotide it is a co-enzyme, which together with an enzyme is essential for several life-sustaining processes (Box 2.2). On reduction it forms the corresponding 1,4-dihydropyridine, NADH, The oxidation of ethanol to acetaldehyde (ethanal) is effected by the enzyme alcohol dehydrogenase and mediated by NAD (Scheme 2.31). 

In addition to enzymes, biological oxidations require substances known as coenzymes. Coenzymes are organic molecules that, in concert with an enzyme, act on a substrate to bring about chemical change. Most of the substances that we call vitamins are coenzymes. The coenzyme contains a functional group that is complementary to a functional group of the substrate the enzyme catalyzes the interaction of these mutually complementary functional groups. If ethanol is oxidized, some other substance must be reduced. This other substance is the oxidized form of the coenzyme nicotinamide adenine dinucleotide (NAD). Chemists and biochemists abbreviate the oxidized form of this... 

There are many examples of second-order reactions in biological systems. The enzyme-catalyzed reaction betweeruthe oxidized form of nicotinamide adenine dinucleotide, NAD, with L-lactic acid can be written as follows... 

Figure 3 Absorbance spectra of the coenzyme nicotinamide adenine dinucleotide in its oxidized (NAD ) and reduced (NADH) forms. (Reproduced with permission from Pineda M and Cardenas J (1998) UV-Visible Spectrophotometry of Biological Compounds (Espectroscopia Ultravioleta-Visible de Compues-tos Biologicos). Cordoba (Spain) Publications of Monte de Pie-dad and Caja de Ahorros of Cordoba.)...

Alternatively, ATP may be produced indirectly. Most biological oxidations involve the removal of hydrogen from a substrate. However, the final combination of hydrogen with oxygen to form water occurs only at the end of a series of reactions. A typical example is the removal of hydrogen coupled to nicotinamide adenine dinucleotide (NAD ), as illustrated in Fig. 9.2 for the oxidation of isocitrate to a-ketoglutarate. 

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