The Mechanism of Deamination

A possible electron circuit in this complex reaction is shown in LXVIII and the products of the completed reaction in LXIX. The rans-arrangement of the hydroxyl on C4 and the aldehyde group (Cl) in LXIX makes the establishment of a furanose ring sterically unlikely and consequently 2,5-anhydro-D-mannose (chitose) probably exists as an ddehydo- ug T. 

Further consideration needs to be given to the interesting fact that although D-glucosaminic acid (2-amino-D-gluconic acid) undergoes de-amination. with the establishment of a 2,5-anhydro ring, the deamination 

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Monoamine oxidase catalyzes the deamination of primary amines and some secondary amines, with some notable exceptions. Aromatic amines with unsubstituted a-carbon atoms are preferred, but aromatic substituents influence the binding of these substrates. For example, m-iodobenzylamine is a good substrate, whereas the o-iodo analog is an inhibitor. The mechanism of deamination is as follows hydrolysis of the Schiff base that results from loss of a hydride ion on an a-proton yields an aldehyde, which is then normally oxidized to the carboxylic acid. Aromatic substrates are probably preferred because they can form a charge-transfer complex with the FAD at the active site, properly... 

Aspects of the mechanism of deamination catalyzed by the nonspecific Takadiastase enzyme are discussed in conjunction with calf duodenal adenosine aminohydrolase (see Section III). 

The mechanism of deamination has been frequently investigated. - Besides ketobascs, phenol and indole derivatives have received partieular... 

The applicability of the Hammond postulate and the Curtin-Hammett principle was discussed in the review of Manuilov and Barkhash (1990) on the mechanism of deamination. This principle allows evaluation of the effect of conformational changes on the reactivity of compounds A and A forming B and B in the kinetic system (7-40), in which the steps with rate constants k and k, may be monomolecular or bimolecular (with a reagent R) A and A are conformers of the starting material. 

Two extensive reviews concerned with the mechanisms of deamination reactions have appeared . White and Woodcock have compared the deamination by nitrous acid to those of the closely related nitrosoamide and triazene decompositions. Ion-pair intermediates were invoked to account for the stereochemistry of the substitution reactions. 

That the reaction given in Fig. 2 for the mechanism of deamination is correct is supported by the failure of the enzyme preparations to deaminate phosphoserine and 0-ethers of serine and the isolation of pyruvic acid from the serine reaction mixtures. "... 

Due to the difficulties in synthesising 8-fluoropurines, scope remains for the exploration of their biological applications. It has been postulated that the electronegative effects of the C-8 fluorine may be significant on the substrate activity of 8-fluoropurine ribosides with enzymes such as N-ribosylhydrolases and transferases [144], The kinetics of 8-fluoroadenosine deamination with calf spleen adenosine deaminase have been measured and compared to adenosine. Since the mechanism of deamination is proposed to proceed via protonation of N-1, it was correctly postulated that the variation in pKa between the N-1 of adenosine (3.59) and 8-fluoroadenosine (2.95) would result in the latter undergoing deamination at a slower rate. 

Isothermal and dynamic studies [1286] of the thermal deamination and racemization reactions of (+)5 9-[Cr(en)3](NCS)3 gave activation energy values 113 and 100 kJ mole"1, respectively. The mechanisms of these and... 

In the light of our present knowledge of the mechanism of these deamination reactions, it can be understood why deamination of either 2-amino-2-deoxy-D-mannonic acid, or the corresponding lactone, gives 2,5-anhydro-D-mannonic acid.39-42... 

The experiments described above indicated amino acids were oxidatively deaminated in liver and their a-amino groups converted to urea. A start on investigations of the mechanism of urea biosynthesis was made by Schultzen and Nenki (1869) who concluded that amino acids gave rise to cyanate which might combine with ammonia from proteins to produce urea. Von Knieren (1873) demonstrated that when he drank an ammonium chloride solution, or gave it to a dog, there was an increase in the formation of urea, without any rise in urinary ammonia. His results were consistent with the cyanate theory but did not eliminate the possibility that urea arose from ammonium carbonate which could be dehydrated to urea ... 

This combination of reactions is known as transdeamination and is the mechanism for deamination of a number of amino acids (Table 8.9). The role of this process in catabolism is shown in Figure 8.10. The ammonia that is prodnced is converted, almost exclnsively, to urea for excretion. Becanse of the biochemical and clinical significance of ammonia, a whole chapter is devoted to it and to urea formation. 

The mechanism of antidepressive action of this series of drugs is likely associated with their inhibition of the oxidizing deamination process of the neurotransmitters norepinephrine, epinephrine, dopamine, and serotonin, which participate in the transmission of nerve excitement in the CNS. A major drawback of these drugs is the high toxicity associated with their inhibition of not only MAO, but also a number of other nonspecific enzymes. 

Nitrosation, diazotation, and deamination processes take place in the reactions resulting in alcohols and N2 gas as final products. From the studies on the pH-dependence of the rate constants at different temperatures, a mechanism was proposed involving diazonium ions as intermediates. With the prediction that coordination to the metal could stabilize the otherwise extremely reactive diazonium species, the mechanism of these reactions are being studied in organic media. 

Deamination. Amine groups can be removed oxidatively via a deamination reaction, which may be catalyzed by cytochromes P-450. Other enzymes, such as monoamine oxidases, may also be involved in deamination reactions (see below). The product of deamination of a primary amine is the corresponding ketone. For example, amphetamine is metabolized in the rabbit to phenylacetone (Fig. 4.27). The mechanism probably involves oxidation of the carbon atom to yield a carbinolamine, which can rearrange to the ketone with loss of ammonia. Alternatively, the reaction may proceed via phenylacetoneoxime, which has been isolated as a metabolite and for which there are several possible routes of formation. The phenylacetoneoxime is hydrolyzed to phenylacetone. Also N-hydroxylation of amphetamine may take place and give rise to phenylacetone as a metabolite. This illustrates that there may be several routes to a particular metabolite. 

Dr. Flaig. The mechanism of the reaction between amino acids and oxidized lignin decomposition products can be described by the scheme of Trautner, which involves oxidative deamination. 

Reactions at the a-carbon atom are affected by the presence of 02. First, by rapidly removing the reducing species, it blocks reductive deamination. This is thought to explain the protective effect of 02 on alanine destruction 26). Secondly, 02 also probably alters the mechanism of oxidative deamination though the products (NH3 and the carbonyl group) are the same 39). 

An effective reagent is aqueous hypophosphorus acid, and an example of its use has been described in detail for the synthesis of 3,3 -dimethylbiphenyl from 4,4 -diamino-3,3 -dimethylbiphenyl (o-tolidine).30 As the latter compound is carcinogenic its preparation is ill-advised. More recently the deamination of diazonium salts with t-butyl nitrite in dimethylformamide has been shown to have wide applicability.31 The reaction proceeds smoothly at 65 °C with the evolution of nitrogen gas, the volume of which may be measured and used to monitor the reaction. The mechanism of the reaction is thought to involve the following radical sequence in which the solvent (DMF = solH), is the hydrogen donor. 

Photooxidation and y-radiolysis agree in their products reasonably well as long as the base is damaged. The reason for this may be that in the photooxidation a dCyd radical cation / menadione radical anion pair is the first intermediate. The reaction of the dCyd radical cation with water could give rise to OH-adducts (as in radiolysis). The most important product, however, is dUrd, that is, deaminated dCyd (Table 10.16) which is not, and cannot be, formed upon radiolysis. The mechanism of its formation is not discussed in the original paper, but it is not unlikely that it results from an unstable intermediate (adduct ) formed in the reaction of the dCyd radical cation / menadione radical anion pair in the solvent cage. 

The presence of a carbonyl substituent in the -position of the hetero-cycle is essential for the cleavage of five-membered rings. The compounds of this type which have been investigated most thoroughly are 3-acylindoles.287, 384-388 At 160-170° 3-acetylindole and hydrazine hydrate give 3-(o-aminophenyl)-5-methylpyrazole, the structure of which was proved by deamination. Other 3-acylindoles, their hydrazones, and azines, react analogously.385 For the mechanism of the reaction see Alberti.384,391 The reaction requires a fourfold excess of hydrazine hydrate,387 preferably a polar solvent,388 and about... 

In addition to being incorporated into tissue proteins, amino acids, after losing their nitrogen atoms by deamination and/or transamination, may be catabolized to yield energy or to form glucose. Conversely, the nonessential amino acids may be synthesized from carbohydrate metabolism intermediates and ammonia or from essential amino acids. This section is devoted to the mechanisms of such metabolic processes and their interrelationships with carbohydrate and lipid metabolic pathways. 

The mechanism of reduction is postulated to involve a 2e reduction of the 1,6 double bond, and immediate 2e reduction of the product, to give 1,2,3,6-tetrahydroadenine. This, in turn, undergoes reductive deamination to form 2,3-dihydropurine, which is further reduced to 1,2,3,6-tetrahydropurine, followed by cleavage of the 2,3 bond with formation of the same diazotizable amine as in purine reduction 153-i6. 162> One reported observation in apparent conflict with this scheme is the detection of purine as an intermediate 1631. On cyclic voltammetry at the H.M.D.F., adenine exhibits a single pH-dependent cathodic peak, with no anodic peak on the return scan 36). 

Babior, B. M., Moss, T. H., Orme-Johnson, W. H., and Beinert, H., 1974, The mechanism of action of edianolamine ammonia-lyase, a B12- dependent enzyme. The participation of paramagnetic species in die catalytic deamination of 2-aminopropanol. J. Biol. Chem. 249 4537n4544. 

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