Oxidation biological mechanisms

Szent-Gyorgyi s early researches concerned the chemistry of cell respiration. He pioneered the study of biological oxidation mechanisms and proved that hex-uronic acid, which he isolated and renamed ascorbic acid, was identical to vitamin C and that it could be extracted from paprika. He won the 1937 Nobel Prize in physiology or medicine for his discoveries, especially of vitamin C. 

According to the proposed mechanism for biological oxidation of ethanol, the hydrogen that is transferred to the coenzyme comes from C-1 of ethanol. Therefore, the dihydropyridine ring will bear no deuterium atoms when CD3CH2OH is oxidized, because all the deuterium atoms of the alcohol are attached to C-2. 

The lack of zinc can also be a problem in biological systems and is responsible for disease states. For example, nitric oxide-dependent apoptosis can be induced in motor neurons by zinc-deficient SOD, and in some cases of amyotrophic lateral sclerosis, zinc-deficient SOD may participate in this type of oxidative mechanism involving nitric oxide.969 One form of hereditary human hair loss or alopecia was mapped to a specific gene and a mutation found in affected individuals. The gene encodes a single zinc finger transcription factor protein with restricted expression in the brain and skin.970 Zinc has been implicated in Alzheimer s via beta amyloid formation, and a role has been attributed for the cerebral zinc metabolism in the neuropathogenesis of Alzheimer s disease.971... 

In the case of the methylated xanthines, particularly theophylline, theobromine and caffeine, the preponderance of data on the metabolism of these compounds in man suggests that a methylated uric acid is the principal product. However, the data presented earlier proposes at best a 77 per cent accounting of the methylated xanthine administered. The question can be raised as to whether the final products observed upon electrochemical oxidation of these compounds aids these studies. Very recently studies of metabolism of caffeine have revealed that 3,6,8-trimethylallantoin is a metabolite of caffeine 48>. This methylated allantoin is, of course, a major product observed electrochemically. The mechanism developed for the electrochemical oxidation seems to nicely rationalize the observed products and electrochemical behavior. The mechanism of biological oxidation could well be very similar, although insufficient work has yet been performed to come to any definite conclusions. There is however, one major difference between the electrochemical and biological reactions which is concerned with the fact that in the former situation no demethylation occurs whereas in the latter systems considerable demethylation appears to take place. 

The initial electrochemical and biological oxidation with xanthine oxidase are essentially identical. However, electrochemically 2,8-dioxyadenine the final product in the presence of xanthine oxidase is much more readily oxidizable than adenine 59) so that considerable further oxidation occurs. To the authors knowledge, 2,8-dioxyadenine is not a major metabolite of adenine in man or other higher organisms. Accordingly, it is likely that other enzymes accomplish further degradation of 2,8-dioxyadenine. The relationship between the products so formed and the mechanism of the reaction to the related electrochemical processes has yet to be studied. 

There is really too little information on the biological oxidation of guanine to attempt to compare it with the electrochemical oxidation. It might be useful to bear in mind the electrochemical mechanism when further studies of the biological oxidation of this compound are carried out. 

It has been suggested that N02 might be formed by the oxidation of nitrite by numerous biological oxidants. Thus, Shibata et al. [90] reported that horse radish peroxidase (HRP) + hydrogen peroxide oxidized nitrite by the following mechanism ... 

Mechanisms of Biological Oxidation and Implications for Multi-Enzyme Biocatalysis... 

Catalytic Oxidation of NAD(P)H A Continuously Improved Selection of Suitable ROMs This research is triggered hy at least two reasons (1) the importance of NAD(P)H/NAD(P)- - redox couples in biological systems is known, as is known the dependence of oxidation mechanisms on the oxidants [14, 82, 172-174] (2) the possibility of developing amperometric biosensors for NAD(P)+-dependent dehydrogenases. As a consequence, much attention is devoted to the regeneration of these coenzymes in their reduced or oxidized forms for their application in biosensors or in enzymatic synthesis [180]. Here, we are concerned with electrochemical regeneration [181]. 

The problems above mostly involve homogeneous oxidations. Another objective of this symposium was to find out how similar are the mechanisms and reactions in homogeneous oxidations to those in heterogeneous catalysis and biological systems. So far it seems that they are not very similar because neither ordinarily involves free radicals. However, the methods used to study biological oxidations have much in common with those used by physical-organic chemists in homogeneous oxidations. 

Most of the numerous other riboflavin-containing enzymes contain FAD. FAD is an integral part of the biological oxidation-reduction system where it mediates the transfer of hydrogen ions from NAD11 to the oxidized cytochrome system. FAD can also accept hydrogen ions directly from a metabolite and transfer them to either NAD, a metal ion, a heme derivative, or molecular oxygen. The various mechanisms of action of FAD are probably due to differences in protein apoenzymes to which it is bound. 

It should be noted that the main amount of redox enzymes in animal and plant cells is accumulated in mitochondria, which are usually called the power plants of the cell, because redox reactions supplying cells with energy proceed in them. Therefore, at present, mitochondria are the main source of information about biological oxidation and energetic conjugation mechanisms. 

Despite the differences between the functions implemented by hydrogen peroxide in gas, liquid and biological oxidation processes, they are united by a specific feature H202 first transforms to a higher reactive form in which the donor-acceptor properties of the original compound are preserved, and then only (in this new form) oxidizes the substrate according to the conjugated mechanism. 

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