Oxidative deamination compounds

Not only does chlordiazepoxide (388) show phototoxicity, but so do two of its metabolites, demethylchlordiazepoxide and demoxepam (389). The first of these is formed by /V-demethylation of the drug and this is followed by oxidative deamination to give demoxepam. Both derivatives therefore retain the IV-oxide group, which proved to be the seat of the phototoxicity. When irradiated in isopropanol at 350 nm for a few minutes, all three compounds gave oxaziridines [10, 225],... 

The biotransformation of clofexamide (4.33, Fig. 4.4), a compound with anti-inflammatory and antidepressant activities, was investigated in rats [18]. About 15% of the dose administered was found in urine as 2-(4-chlorophe-noxy)acetic acid (4.37). This metabolite was formed via the secondary amine 4.34, the primary amine 4.35, and the acid 4.36 resulting from oxidative deamination. However, direct formation of 2-(4-chlorophenoxy)acetic acid (4.37) from the parent compound (4.33) cannot be excluded. Clofexamide and its metabolite 4.34 also underwent hydroxylation on the aromatic ring, but these hydroxylated metabolites did not appear to be hydrolyzed. 

A 1-Pyrroline has been prepared in low yield by oxidation of proline with sodium hypochlorite,102 persulfate,166 and periodate.167 The best procedure for the preparation of A 1-pyrroline and A 1-piperideine consists of dehydrohalogenation of A-chloropyrrolidine and A-chloro-piperidine, which are readily accessible by chlorination with feri-butyl hypochlorite.168 A 1-Pyrroline and A piperideine are products of enzymic oxidative deamination of putrescine and cadaverine, or ornithine and lysine, respectively.169,170 This process plays an important part in metabolism and in the biosynthesis of various heterocyclic compounds, e.g. alkaloids. 

AMINO ACID INTERCONVERSIONS Little is known of the precise amino acid requirements of cestodes. Presumably, most, if not all, their required amino acids can be provided by the host and, as discussed above, cestodes have developed numerous transport systems to acquire these compounds. However, cestodes appear to have a limited ability to catabolise amino acids. This is exemplified by H. diminuta, which has been shown (918) to generate significant 14C02 only from relabelled aspartate and, to a lesser extent, alanine during incubation in vitro with 10 different amino acids (Table 6.6). The few amino acids that are catabolised in cestodes participate in two main pathways, namely transamination and oxidative deamination. 

The biological function of amine oxidases involves the oxidation of biogenic amines formed during normal biological processes. In mammals, the monoamine oxidases are involved in the control of the serotonin catecholamine ratios in the brain, which in turn influence sleep and EEG patterns, body temperature, and mental depression. Two groups of amine oxidases are involved in the oxidative deamination of naturally occurring amines as well as foreign compounds. 

Fig. 1. a-Oxidation of amino acids. Hydroxyl radical (or other reactive radical) abstracts hydrogen atom from the a-carbon. The C-centered free radical formed may react with other amino acid residues or dimerize in the absence of oxygen, which leads to protein aggregation. In die presence of oxygen the carbon-centered radical forms peroxyl radical. Reduction of peroxyl radical leads to protein hydroperoxide. Decomposition of hydroperoxide leads to formation of carbonyl compounds via either oxidative deamination or oxidative decarboxylation. Oxidation of the new carbonyl group forms a carboxyl group. 

Diphenylhydrazine is oxidized to diphenylnitrosamine (50%) by potassium superoxide. The same reagent also oxidizes 1-methyl-1-phenylhydrazine, but here the nitrosamine is a minor product the major reaction is deamination. A better meAod of oxidative deamination of some 1,1-disubstituted hydrazines and hydrazinium salts is reaction with nitrous acid. Thus, several hydrazinium salts MezRN NHi X were deaminated to the tertiary amine by treatment with nitrous acid. The method has also been used to deaminate IV-aminoheterocyclic compounds for example, some 1,2,3-triazoles are conveniently prepared by deamination of the corresponding 1-aminotriazoles with nitrous acid. °... 

Reaction with ninhydrin Ninhydrin is a strong oxidizing agent. When a solution of amino acid is boiled with ninhydrin, the amino acid is oxidatively deaminated to produce ammonia and a ketoacid. The keto acid is decarboxylated to produce an aldehyde with one carbon atom less than the parent amino acid. The net reaction is that ninhydrin oxidatively deaminates and decarboxylates a-amino acids to C02, NH3 and an aldehyde. The reduced ninhydrin then reacts with the liberated ammonia and another molecule of intact ninhydrin to produce a purple coloured compound known as Ruhemann s purple. 

The dominant reactions involved in removing amino acid nitrogen from the body are known as transaminations. This class of reactions funnels nitrogen from all free amino acids into a small number of compounds then, either they are oxidatively deaminated, producing ammonia, or their amine groups are converted to urea by the urea cycle. 

Secondary and Primary Amines. Secondary amines (cither patent compounds or metabolites) are susceptible to oxidative N-dealkylation. oxidative deamination, and N-oxi-dation reactions. - As in tertiary aminc.s. N-dealkylation of secondary amines proceeds by the carbinolamine path-... 

The acetylation of some primary aliphatic amines such as histamine. mescaline. and the bis-N-demethylated metabolite of of-j-methadol" "" also has been reported. In comparison with oxidative deamination processes. N-acetylation is only a minor pathway in the metabolism of this cla.ss of compounds. 

P-450s carry out aliphatic and aromatic hydroxylat-ions, aromatic epoxidations (leading to stable epoxides like dieldrin from aldrin, or arene oxides), 0-, N-, and S-dealkylations and oxidations, oxidative deaminations, and desulfurations among other reactions. Although the primary evolutionary role of the P-450 enzymes is to convert hydrophobic xenobiotics into more hydrophilic compounds and enhance their removal from the body, P-450s also catalyze reactions that lead to more reactive (and hence toxic) compounds. Several xenobiotics are converted into potential carcinogens via the cytochrome P-450 system. 

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