Biological redox reactions

The reactive center in NADH (highlighted in orange) functions as a hydride delivery agent (very much like NaBH4 or LAH) and can reduce ketones or aldehydes to form alcohols. NADH acts as a reducing agent, and in the process, it is oxidized. The oxidized form is called NAD.  

The reverse process can also occur. That is, NAD can act as an oxidizing agent by accepting a hydride from an alcohol, and in the process, NAD is reduced to give NADH. 

To remember which is the reducing agent and which is the oxidizing agent, simply remember that NADH has an H at the end of its name, because it can function as a delivery agent of hydride. 

NADH and NAD play an important role in the citric acid cycle as well as in ATP synthesis. 

The enzyme that catalyzes this oxidation process is called alcohol dehydrogenase. Methanol is oxidized twice. The first oxidation produces formaldehyde, while the second oxidation produces formic acid. Formic acid is highly toxic, even in small quantities. A buildup of formic acid in the eyes leads to blindness, and a buildup of formic acid in other organs leads to organ failure and death. 

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Ravindranath and co-workers studied the electrochemical behavior of 5-amino-2-phenyl-4-arylazo-l,2-dihydro-3//-pyrazol-3-one (90UC864) and 5-methyl-4-arylazo-2-(pyridin-2-ylcarbonyl)-2,4-dihydro-3//-pyrazol-3-(Mie (90IJC895). Similar studies were undertaken by Jain and Damodharan of pyrazol-3-ones 408a-f (95CJC176) (Scheme 94). The underlying rationale for this study on the electrochemical reduction of these biologically important pyrazol-3-ones is that it can lead to information on the reaction routes and mechanisms of biological redox reactions. 

Flavin Adenine Dinucleotide (FAD) (C27 H33 N9 O15P2) is a coenzyme that acts as a hydrogen acceptor in dehydrogenation reactions in an oxidized or reduced form. FAD is one of the primary cofactors in biological redox reactions. 

It is thus possible to calculate the free-energy change for any biological redox reaction at any concentrations of the redox pairs. 

G. Dryhurst and co-workers have investigated the electrochemistry of naturally occurring JV-heterocyclic molecules, including uric acid, xanthine, adenine, and guanine,5,402 in the expectation that the mechanisms observed electrochemically might lead to a more detailed understanding of the biological redox reactions of these molecules. 

Acid catalysis is also effective for enhancing the oxidizing ability of the excited states of flavins [59], which are important coenzymes in the biological redox reactions [60-62], Flavin analogs (FI) are known to be protonated at the N - 1 position in a strongly acidic aqueous solution (pK.-ca.0K63] ... 

Pterin coenzymes such as folic acid (pteroylglutamic acid) and biopterin, which contain a dicyclic pteridine ring, a part of the skeleton of flavins, are also known to play versatile roles in biological redox reactions [67]. The oxidizing ability of the excited state of a pteridine derivative (lumazine [Lu])... 

Nicotinamide coenzymes act as intracellular electron carriers to transport reducing equivalents between metabolic intermediates. They are cosubstrates in most of the biological redox reactions of alcohols and carbonyl compounds and also act as cocatalysts with some enzymes. 

Deng, H., and Van Berkel, G. J. (1999). A thin-layer electrochemical flow cell coupled online with electrospray-mass spectrometry for the study of biological redox reactions. 

Buvet, R. 1983. General criteria for the fulfilment of redox reactions. In G. Milazzo, and M. Blank, Eds., Bioelectrochemistry 1. Biological Redox Reactions, pp. 15-50, Plenum, New York. 

There has been much speculation regarding the mode of action of sulfur. The current view is that sulfur itself (Sg) may be toxic to fungi. Recent smd-ies indicate that sulfur is not biological inert and probably becomes involve in biological redox reactions. These studies also suggest that sulfur can more easily penetrate spores in the presence of urea, hydrocarbons, surfactants, and lime. 

Acid catalysis is also effective for the electron transfer reduction of flavins, which are also important coenzymes in the biological redox reactions [80-82], Flavin analogues (FI la and lb) are known to be protonated at the N-1 position in a strongly acidic aqueous solution as shown in Scheme 5 (pa s 0) [83]. In an aprotic solvent such as acetonitrile (MeCN), the protonation of FI occurs much more readily than in H2O [84]. The one-electron reduced radical FIH can also be protonated to give F1H2 + in acetonitrile (Scheme 5) [84]. In such a case, an acid-catalyzed electron transfer from 6W-[R2Co(bpy)2] to F1H+ in MeCN occurs to yield F1H2 (Eq. 7) [84] ... 

Metalloporphyrins can also act efficient catalysts in a variety of chemical and biological redox reactions. This area has been extensively studied and the catalytic functions of metalloporphyrins via electron transfer reactions have been reviewed Volume II, Part 2, Chapter 8 [270]. 

Volk, K.J. Yost, K.A. Brajter-Toth, A. Electrochemistry on Line with Mass Spectrometry. Insight into Biological Redox Reactions, Anal. Chem. 64, 21-23 (1992). 

Electron transport is by virtue of a reversible valency change of the inorganic heme iron the main biological function of the cytochromes in various biological redox reactions (e.g. respiration, photosynthesis). The porphyrin ligand can always participate in the sequence of reactions. 

In biological redox reactions, electrons are transferred to electron acceptors such as the nucleotide NAD+/NADH (nicotinamide adenine dinucleotide in its oxi-dized/reduced form). 

Cummins, P., Geeady, J. (1989) Mechanistic Aspects of Biological Redox Reactions Involving NADH 1 ab initio Quantum Chemical Structure of the 1-Methyl-nicotinamide and 1-Methyl-Dihydronicotinamide Coenzyme Analogues, J. Mol. Struct. (Theochem) 183, 161-174. 

Experimental investigation of the factors that control the rates of biological redox reactions has not come as far as the study of the electron transfers of metal complexes, because many more variables must be dealt with (e.g., asymmetric surface charge, nonspherical shape, uncertain details of structures of proteins complexed with small molecules or other proteins). Many experimental approaches have been pursued, including the covalent attachment of redox reagents to the surfaces of metalloproteins. 

Single electron transfer generates radicals and although this mechanism is now more common than once thought in non-biological redox reactions, its prevalence in enzyme-catalysed reactions is limited to coenzymes with quinoid-type structures e.g. flavins, coenzyme Q, vitamins C, E and K and to enzymes containing transition metals. Of course, there is a growing interest in metabolic disorders initiated by radical reactions. Reduction by 2-electron transfer can take place by either (a) hydride, H, transfer or (b) discrete electron, e , and proton, H", addition. 

An example of an oxidation-reduction reaction is the one that occurs when a strip of metallic zinc is placed in an aqueous solution containing copper ions. Although both zinc and copper ions play roles in life processes, this particular reaction does not occur in living organisms. However, it is a good place to start our discussion of electron transfer because, in this comparatively simple reaction, it is fairly easy to follow where the electrons are going. (It is not always quite as easy to keep track of the details in biological redox reactions.) The experimental observation is that the zinc metal disappears and zinc ions go into solution, while copper ions are removed from the solution and copper metal is deposited. The equation for this reaction is... 

This reaction is a particularly clear example of electron transfer. It will be useful to keep these basic principles in mind when we examine the flow of electrons in the more complex redox reactions of aerobic metabolism. In many of the biological redox reactions we will encounter, the oxidation state of a carbon atom changes. Figure 15.2 shows the changes that occur as carbon in its most reduced form (an alkane) becomes oxidized to an alcohol, an aldehyde, a carboxylic acid, and ultimately carbon dioxide. Each of these oxidations requires the loss of two electrons. 

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