Ammonia production, metabolic reactions

Urea ((NH2)2CO), a small and highly water soluble molecule, is an end product of amine and ammonia nitrogen metabolism and as such represents an example of biodetoxification (Section 6.4). The process is discussed in this section because it illustrates a genuine de novo biosynthetic pathway rather than detoxification involving chemical modification, via phase I and phase II reactions, of a pre-existing molecule as is the case for haem or steroid hormones. 

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. 

Fig. 1.8 Asaccharolytic fermentation produces ammonia and short-chain fatty acids. This group of fermentations by oral bacteria utilizes proteins, which are converted to peptides and amino acids. The free amino acids are then deaminated to ammonia in a reaction that converts nicotinamide adenine dinucleotide (NAD) to NADH. For example, alanine is converted to pyruvate and ammonia. The pyruvate is reduced to lactate, and ammonium lactate is excreted into the environment. Unlike lactate from glucose, ammonium lactate is a neutral salt. The common end products in from plaque are ammonium acetate, ammonium propionate, and ammonium butyrate, ammonium salts of short chain fatty acids. For example, glycine is reduced to acetate and ammonia. Cysteine is reduced to propionate, hydrogen sulfide, and ammonia alanine to propionate, water, and ammonia and aspartate to propionate, carbon dioxide, and ammonia. Threonine is reduced to butyrate, water, and ammonia and glutamate is reduced to butyrate, carbon dioxide, and ammonia. Other amino acids are involved in more complicated metabolic reactions that give rise to these short-chain amino acids, sometimes with succinate, another common end product in plaque.

Ammonia arises in the body principally from the oxidative deamination of amino acids. In addition to its uptake in the reactions mentioned above, ammonia is also excreted in the urine as ammonium salts. This is not derived directly from the blood ammonia but is formed by the kidney from glutamine by the action of glutaminase. In metabolic acidosis, ammonia production and excretion by the kidney is greatly increased, and conversely it is decreased in metabolic alkalosis. This may be an important means of excreting excess ammonia. It must be remembered that ammonia formed by the action of intestinal bacteria on the protein hydrolyzates in the intestine can be also absorbed. The contribution of the ammonia formed in this way to the total ammonia in the body is unknown. Since this ammonia drains into the portal circulation, it is promptly removed by the liver. 

While the results of the growth reversal experiments in the "supercomplex systems" described above had stimulated investigations at the level of "defined systems" (i.e. the examination of certain metabolic reactions in cell-free systems), no definitive answers as to the biochemical mode of action of glyphosate had been obtained. Based on our experience with inhibitors of phenylalanine ammonia-lyase (see below), we included the "complex system" level (i.e. the examination of a metabolic pathway jsi vivo) in our strategy in order to define the limits more closely. Hypocotyls from etiolated buckwheat seedlings provided a system in which the rapid synthesis of phenylalanine-derived products, such as anthocyanin and other phenylpropanoid compounds, can be very simply induced by illumination. Anthocyanins, in particular, can be conveniently extracted and quantified and, at least in buckwheat, are not subject to measurable turnover within... 

Such reversible reactions are key to certain industrially important processes such as the synthesis of ammonia and the production of sulfuric acid. They are also crucial in our body chemistry. The reversible nature of so many metabolic reactions in our biochemistry means that these reactions can be controlled by subtle changes in conditions. For instance, reversible effects control how oxygen binds to, and is released from, the hemoglobin in red blood cells as they flow through our lungs and other tissues of our body. The complexity of our body chemistry is dependent on the fine control that is possible where the metabolic pathways consist of sequences of reversible reactions. 

Diomides. These compds are the dibasic acid derivs of ammonia or amines, and contain two -CONH2 groups. Numerous combinations of diacids, diamines, and amino acids have been interacted. Copolymers contg various proportions of two or more diacids have been prepd (Ref 2). The diamide of carbonic acid is called urea, H2NCONH2. It is a product of animal metabolism and is prepd industrially by reaction of CO2 with excess NH3 at high temp, or by an older method involving the hydrolysis of cyanamide (Ref 5)... 

Nevertheless, malonyl-CoA is a major metabolite. It is an intermediate in fatty acid synthesis (see Fig. 17-12) and is formed in the peroxisomal P oxidation of odd chain-length dicarboxylic acids.703 Excess malonyl-CoA is decarboxylated in peroxisomes, and lack of the decarboxylase enzyme in mammals causes the lethal malonic aciduria.703 Some propionyl-CoA may also be metabolized by this pathway. The modified P oxidation sequence indicated on the left side of Fig. 17-3 is used in green plants and in many microorganisms. 3-Hydroxypropionyl-CoA is hydrolyzed to free P-hydroxypropionate, which is then oxidized to malonic semialdehyde and converted to acetyl-CoA by reactions that have not been completely described. Another possible pathway of propionate metabolism is the direct conversion to pyruvate via a oxidation into lactate, a mechanism that may be employed by some bacteria. Another route to lactate is through addition of water to acrylyl-CoA, the product of step a of Fig. 17-3. Tire water molecule adds in the "wrong way," the OH ion going to the a carbon instead of the P (Eq. 17-8). An enzyme with an active site similar to that of histidine ammonia-lyase (Eq. 14-48) could... 

Some of the pathways of animal and bacterial metabolism of aromatic amino acids also are used in plants. However, quantitatively more important are the reactions of the phenylpropanoid pathway,173-1743 which is initiated by phenylalanine ammonia-lyase (Eq. 14-45).175 As is shown at the top of Fig. 25-8, the initial product from phenylalanine is trails-cinnam-ate. After hydroxylation to 4-hydroxycinnamate (p-coumarate) and conversion to a coenzyme A ester,1753 the resulting p-coumaryl-CoA is converted into mono-, di-, and trihydroxy derivatives including anthocyanins (Box 21-E) and other flavonoid compounds.176 The dihydroxy and trihydroxy methylated products are the starting materials for formation of lignins and for a large series of other plant products, many of which impart characteristic fragrances. Some of these are illustrated in Fig. 25-8. 

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