Electron transfer metabolism

Lipoic acid is an acyl group carrier. It is found in pyruvate dehydrogenase zard a-ketoglutarate dehydrogenase, two multienzyme complexes involved in carbohydrate metabolism (Figure 18.34). Lipoie acid functions to couple acyl-group transfer and electron transfer during oxidation and decarboxylation of a-keto adds. 

Redox reactions can proceed by direct transfer of electrons between chemical species. Examples include the rusting of iron and the metabolic breakdown of carbohydrates. Redox processes also can take place by indirect electron transfer from one chemical species to another via an electrical circuit. When a chemical reaction is coupled with electron flow through a circuit, the process is electrochemical. Flashlight batteries and aluminum smelters involve electrochemical processes. 

Reported redox potentials of laccases are lower than those of non-phenolic compounds, and therefore these enzymes cannot oxidize such substances [7]. However, it has been shown that in the presence of small molecules capable to act as electron transfer mediators, laccases are also able to oxidize non-phenolic structures [68, 69]. As part of their metabolism, WRF can produce several metabolites that play this role of laccase mediators. They include compounds such as /V-hvdi oxvacetan i I ide (NHA), /V-(4-cyanophenyl)acetohydroxamic acid (NCPA), 3-hydroxyanthranilate, syringaldehyde, 2,2 -azino-bis(3-ethylben-zothiazoline-6-sulfonic acid) (ABTS), 2,6-dimethoxyphenol (DMP), violuric acid, 1-hydroxybenzotriazole (HBT), 2,2,6,6-tetramethylpipperidin-iV-oxide radical and acetovanillone, and by expanding the range of compounds that can be oxidized, their presence enhances the degradation of pollutants [3]. 

The antagonists of nicotinic acid are 6-aminonicotinamide and, less potent, 3-acetylpyridine and pyridine-3-sulfonic acid (H15, J4). Nicotinamide has also been reported to be effective in experimental cancer (S3). It is supposedly converted to nonphysiological nucleotide analogs of NAD and NADP because it becomes attached to available apo-dehydrogenase the resulting enzyme cannot function in hydrogen and electron-transfer reactions essential to normal cellular metabolism (D7). 

Iron is an essential cofactor of numerous enzymes, involved in, for instance, electron transfer and oxygen metabolism. It seems counterintuitive that the fourth most abundant element in the biosphere is in many instances the least bioavailable bioelement and therefore the limiting growth factor. The reason for this lies in the extremely low solubility of ferric iron (Fe3+) the prevailing form of iron under oxic conditions. Iron is precipitated as Fe(OH)3 with a solubility product of 10 39, which limits the aqueous concentration of ferric ion... 

Since many of the transformations undergone by metabolites involve changes in oxidation state, it is understandable that cofactors have been developed to act as electron acceptors/ donors. One of the most important is that based on NAD/NADP. NAD+ can accept what is essentially two electrons and a proton (a hydride ion) from a substrate such as ethanol in a reaction catalysed by alcohol dehydrogenase, to give the oxidized product, acetaldehyde and the reduced cofactor NADH plus a proton (Figure 5.2). Whereas redox reactions on metal centres usually involve only electron transfers, many oxidation/reduction reactions in intermediary metabolism, as in the case above, involve not only electron transfer but... 

Group-transfer reactions often involve vitamins3, which humans need to have in then-diet, since we are incapable of realizing their synthesis. These include nicotinamide (derived from the vitamin nicotinic acid) and riboflavin (vitamin B2) derivatives, required for electron transfer reactions, biotin for the transfer of C02, pantothenate for acyl group transfer, thiamine (vitamin as thiamine pyrophosphate) for transfer of aldehyde groups and folic acid (as tetrahydrofolate) for exchange of one-carbon fragments. Lipoic acid (not a vitamin) is both an acyl and an electron carrier. In addition, vitamins such as pyridoxine (vitamin B6, as pyridoxal phosphate), vitamin B12 and vitamin C (ascorbic acid) participate as cofactors in an important number of metabolic reactions. 

Another interesting response in hydrogen metabolism was observed by Hoch et al. [27] They found that N2-fixing organisms exposed to D2 in the presence of N2 formed HD. They referred to this as an exchange reaction. Later Bulen [28] indicated that it was improper to refer to this as an exchange reaction as it involved electron transfer. He also pointed to the factors in common between H2 inhibition and HD formation. 

Figure 1. Simplified scheme for the electron transfer in the Cytochrome P-450 mediated monooxygenase activity. In the liver, the fiavoprotein is Cystochrome c reductase. R is the compound being metabolized. NAD and Cytochrome bs have...

The electron transfer system has not been studied in detail in fish, but the metabolism of compounds such as biphenyl (37), benzo(a)pyrene (21) and 2,5-diphenyloxazole (38) by fish liver microsomes has been shown to require oxygen and NADPH generating system. The metabolism of BP (21), 2,5-diphenyloxazole (Ahokas, unpublished observation) and aldrin (27.) by fish liver microsomal enzyme system is inhibited strongly by carbon monoxide. This information and the fact that cytochrome P-1+50, as well as NADPH cytochrome c reductase system are present in fish, suggest strongly that fish have a cytochrome P-1+50 mediated monooxygenase system which is very similar to that described in mammals. 

Dihaloelimination is a two-electron transfer reaction. Thompson et al. [377] reported reductive dichloroelimination of 1,1,2-TCA and TeCA by hepatic micro-somes from rat Ever, with VC and both tDCE and cDCE as metabolites. Reductive dichloroelimination from hexa- and pentachloroethane by microsomal cytochrome P450 was studied by Nastainczyk et al. [378]. The main products of the in vitro metabolism of hexa- and pentachloroethane were PCE (99.5%) and TCE (96%), respectively, with minor amounts of pentachloroethane (0.5%) and TeCA (4%), respectively, via reductive dechlorination. 

Two basic problems face the cell in controlling energy flow via coupled electron transfer reactions [1, 2], The first involves controlling the rates of these processes, so that a level of electron flow appropriate to the metabolism of the cell can be maintained. 

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