Hydrogen transport coenzymes

What hydrogen-transporting coenzymes play important roles in the oxidation of fatty acids ... 

Most coenzymes have aromatic heterocycles as major constituents. While enzymes possess purely protein structures, coenzymes incorporate non-amino acid moieties, most of them aromatic nitrogen het-erocycles. Coenzymes are essential for the redox biochemical transformations, e.g., nicotinamide adenine dinucleotide (NAD, 13) and flavin adenine dinucleotide (FAD, 14) (Scheme 5). Both are hydrogen transporters through their tautomeric forms that allow hydrogen uptake at the termini of the quinon-oid chain. Thiamine pyrophosphate (15) is a coenzyme that assists the decarboxylation of pyruvic acid, a very important biologic reaction (Scheme 6). 

In further experiments (Jam et ci., 1944) it was shown that, with barley saps to which hexose diphoqihate and ascorbic acid were added, an increased oxygen uptake occurred in excess of that caused by the addition of ascorbic acid alone. This oxygen uptake could be still further increased by the addition of coenzyme I. The breakdown of hexose diphosphate to phosphoglyceric acid which was observed was stimulated by the addition of ascorbic acid. The course of hydrogen transport was therefore believed to be triose phosphate —> coenzyme I ascorbic acid — Oj. 

B2 (riboflavin) Milk, meat, eggs, dark green vegetables, bread, beans, peas Forms the coenzymes FMN and FAD, which are hydrogen transporters Dermatitis (skin problems)... 

The next step of great significance was the discovery of Warburg and his groups that the amide of nicotinic acid was part of coenzyme II (TPN, NADP) and functionally essential for the hydrogen-transporting role of this coenzyme, shortly followed by a parallel finding by Von Euler et al. in coenzj me I (DPN, NAD). 

Besides DPN, a number of other coenzymes of the oxido-reduction type act by reason of their ability to be alternatively oxidized and reduced. These are the coenzymes of hydrogen transport TPN, FMN, FAD and thioctic acid, whose structure we have already considered. 

DPN and TPN are the major coenzymes involved in hydrogen transport at the substrate level. Their main function appears to be to remove hydrogen from certain substrates (in cooperation with the proper dehydrogenases) and to transfer the hydrogen (or electron) to another coenzyme in the hydrogen transport series, or to another substrate, which is accordingly reduced. 

The flavin-containing coenzymes are similar in importance to the pyridine coenzymes as functioning in hydrogen transport. In general the flavin coenzymes mediate hydrogen transport between coenyzmes, rather than between substrates, although their function in anaerobic bacteria and certain other tissues indicates that they may also play an important role in hydrogen transport at the substrate level. 

This observation apparendy could not be explained without postulating hydrogen transport between NADP and NAD. However, in contrast to the mitochondria, the respective enzyme enabling the direct transfer of hydrogen from NADH to NADP in the cytoplasm was not so far described. In addition, as we have already stated, the ratios of the reduced forms of the coenzymes to the oxidized ones are in favor of NADPH and the transfer of hydrogen from NADH to NADP is energy dependent, even if it is an indirect transfer (Flatt and Ball, 1965). There is no absolute evidence, however, that NADH could not be direcdy utilized in the liver for the fatty acid synthesis. 

Biochemical role. Nicotinamide functions as a constituent of the pyridine nudeo-tides, which occupy a central role as hydrogen-transferrii coenzymes (transport metabolites for hydrogen). 

FIGURE 18.13 In electron transport, coenzymes NADH and FADH2 are oxidized in enzyme complexes providing electrons and hydrogen ions for ATP synthesis. 

Lipoic acid, or 6,8-dithiolane octanoic acid, is widely distributed in living organisms, intervening in hydrogen transport and acyl radicals by acting as a necesssary coenzyme in the oxidative decarboxylation of pyruvate. If one considers the electrochemical oxidation of the lipoic acid at the surface of the carbon paste electrode (EPC), in contrast to cystine, the molecule is electroactive at potentials less positive than +1.0 V vs SCE. The voltammetric recordings show a perfectly defined oxidation peak which indicates a fast kinetic reaction Ep - Ep/2 = 50 mV. 

Whatever the explanation of the lesser activities of the coenzymes, the observation that their lesser activity in growth parallels that found in their metabolic stimulation is of value in emphasizing that the two processes are closely interdependent. A further correlation of this type is afforded by the observation (47) that nicotinic acid is unable to replace nicotinamide, both in growth and in hydrogen transport (from glucose to methylene blue), by PasteureUa suiseptica. The acid can replace the amide in both activities in related organisms (102). 

Coenzymes serve as recyclable shuttles—or group transfer reagents—that transport many substrates from their point of generation to their point of utilization. Association with the coenzyme also stabilizes substrates such as hydrogen atoms or hydride ions that are unstable in the aqueous environment of the cell. Other chemical moieties transported by coenzymes include methyl groups (folates), acyl groups (coenzyme A), and oligosaccharides (dolichol). 

Ubiquinone, known also as coenzyme Q, plays a crucial role as a respiratory chain electron carrier transport in inner mitochondrial membranes. It exerts this function through its reversible reduction to semiquinone or to fully hydrogenated ubiquinol, accepting two protons and two electrons. Because it is a small lipophilic molecule, it is freely diffusable within the inner mitochondrial membrane. Ubiquinones also act as important lipophilic endogenous antioxidants and have other functions of great importance for cellular metabolism. ... 

Most compounds oxidized by the electron transport chain donate hydrogen to NAD+, and then NADH is reoxidized in a reaction coupled to reduction of a flavoprotein. During this transformation, sufficient energy is released to enable synthesis of ATP from ADP. The reduced flavoprotein is reoxidized via reduction of coenzyme Q subsequent redox reactions then involve cytochromes and electron transfer processes rather than hydrogen transfer. In two of these cytochrome redox reactions, there is sufficient energy release to allow ATP synthesis. In... 

Free energy is released as electrons are transferred along the electron transport chain from an electron donor (reducing agent or reduc-tant) to an electron acceptor (oxidizing agent or oxidant). The (electrons can be transferred in different forms, for example, as hydride ions ( FT) to NAD+, as hydrogen atoms (-H) to FMN, coenzyme Q, and FAD, or as electrons (-e ) to cytochromes. 

Keilin soon realized that three of the absorption bands, those at 604,564, and 550 nm (a, b, and c), represented different pigments, while the one at 521 nm was common to all three. Keilin proposed the names cytochromes a, b, and c. The idea of an electron transport or respiratory chain followed6 quickly as the flavin and pyridine nucleotide coenzymes were recognized to play their role at the dehydrogenase level. Hydrogen removed from substrates by these carriers could be used to oxidize reduced cytochromes. The latter would be oxidized by oxygen under the influence of cytochrome oxidase. 

Figure 12.36 shows the reduction reaction of coenzyme Q into the reduced form, QFI2. The added hydrogens are shown in blue. QF12 is the energized form that can feed into the electron transport chain to synthesize ATP. 

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