Ammonium ions excretion

Latorre, C., Lee, J.H., Spiller, H. and Shanmugan, K.T. 1986. Ammonium ion-excreting cyanobacterial mutant as a source of nitrogen for growth of rice a feasibility study. Biotech. Lett., 8, 507-512. 

There have been many anecdotal reports of metabolic acidosis in glue sniffers, attributed to renal tubular acidosis. However, it has been suggested that it is in fact due to overproduction of hippuric acid resulting from the metabolism of toluene, with or without a reduced rate of urinary ammonium ion excretion (32). 

Fig. 42.6. Renal glutamine metabolism. Renal tubule cells preferentially oxidize glutamine. During metabolic acidosis, it is the major fuel for the kidney. Conversion of glutamine to a-ketoglutarate generates NH4. Ammonium ion excretion helps to buffer systemic acidemia.

The stimulus to production of ammonia is intracellular acidosis in renal tubular cells. When an acidosis develops and persists, the rate of ammonia production by the renal tubular cells increases over the course of several days. This is due to induction of the enzyme glutaminase (i.e. the production of new enzyme). The rate of production of ammonia provides a homeostatic mechanism in the excretion of excess acid from the body. As is shown in Figure 7.4, in chronic metabolic acidosis the rate of ammonium ion excretion in the urine at a given urine pH is more than double the rate in a healthy person (Pitts, 1948). 

Amino groups released by deamination reactions form ammonium ion (NH " ), which must not escape into the peripheral blood. An elevated concentration of ammonium ion in the blood, hyperammonemia, has toxic effects in the brain (cerebral edema, convulsions, coma, and death). Most tissues add excess nitrogen to the blood as glutamine. Muscle sends nitrogen to the liver as alanine and smaller quantities of other amino acids, in addition to glutamine. Figure I-17-1 summarizes the flow of nitrogen from tissues to either the liver or kidney for excretion. The reactions catalyzed by four major enzymes or classes of enzymes involved in this process are summarized in Table T17-1. 

Rabbits form bicarbonate in the gut and absorb it. They do not have to form new bicarbonate in the kidneys and need not excrete ammonium ions in the urine, but they still need to excrete organic anions. These organic anions are accompanied in the urine by sodium or potassium ions, which can generate a severe negative sodium balance for the period that the rabbits are on a browse diet(Iason and Palo, 1991). Therefore, lagomorphs excrete biotransformational... 

Ammonia (NH3) is a relatively strong base, and at physiological pH values it is mainly present in the form of the ammonium ion NH4 (see p. 30). NH3 and NH4 are toxic, and at higher concentrations cause brain damage in particular. Ammonia therefore has to be effectively inactivated and excreted. This can be carried out in various ways. Aquatic animals can excrete NH4 directly. For example, fish excrete NH4 via the gills (ammonotelic animals). Terrestrial vertebrates, including humans, hardly excrete any NH3, and instead, most ammonia is converted into urea before excretion ureotelic animals). Birds and reptiles, by contrast, form uric acid, which is mainly excreted as a solid in order to save water uricotelic animals). 

Ammonia can diffuse freely into the urine through the tubule membrane, while the ammonium ions that are formed in the urine are charged and can no longer return to the cell. Acidic urine therefore promotes ammonia excretion, which is normally 30-50 mmol per day. In metabolic acidosis (e.g., during fasting or in diabetes mellitus), after a certain time increased induction of glutaminase occurs in the kidneys, resulting in increased NH3 excretion. This in turn promotes H"" release and thus counteracts the acidosis. By contrast, when the plasma pH value shifts towards alkaline values alkalosis), renal excretion of ammonia is reduced. 

Ammonia (NH3) and the ammonium ion (NH4"1") are highly toxic to mammalian cells. In vivo, ammonium is secreted by the cells and transported to the mitochondria of hepatocytes, where it is converted into urea via the urea cycle. Urea production occurs almost exclusively in the liver and is the fate of most of the ammonium channeled there. The urea passes into the bloodstream and thus to the kidneys and is excreted into the urine. Mammalian cells in culture secrete ammonium into the culture medium, where its concentration increases gradually because there is no ammonium recycling pathway (Newland et al., 1990). 

When ammonia enters the body, it is converted to urea and excreted by the kidneys. The capacity for detoxification via urea is sufficient to eliminate the ammonium ion when ammonia is inhaled in non-irritating concentrations. Repeated inhalation can cause a higher tolerance because the mucous membranes become increasingly resistant. Ammonia is not considered to be carcinogenic nor is it mutagenic. The effects of different ammonia concentrations are summarized in Table 8.374. 

In humans and many other vertebrates, ammonia arising from deamination reactions or other sources is excreted in the form of urea. These animals are called ureo-telic. Fish excrete nitrogen in the form of ammonium ions and are therefore ammonotelic. Animals that need to conserve water excrete their nitrogen in the form of crystalline uric acid. They are uricotelic, or purinotelic. One often finds animals that convert uric acid to allantoin via uric acid oxidase (Figure 20.8). Allan-toin is more water soluble than uric acid. Uric acid oxidase is absent from primates. 

The glutamine synthase reaction is important in several respects. First, it produces glutamine, one of the 20 major amino acids. Second, in animals, glutamine is the major amino acid found in the circulatory system. Its role is to carry ammonia to and from various tissues, but principally from peripheral tissues to the kidney, where the amide nitrogen is hydrolysed by the enzyme glutaminase (reaction below) this process regenerates glutamate and free ammonium ion, which is excreted in the urine. 

FJGURE, 20 Eliminiitian of ammonium ions via the urea cycle or via direct excretion. With protein catabolism, the excretion of wafste nitrogen via the urea cycle results in net prod union of acid in the body however, excretion of ammonium ions by the kidney into the urine does not result in this production of acid in the body. 

---