Kidney glutaminases

Muntwyler E, lacobellis M, Griffin GE. 1956. Kidney glutaminase and carbonic anhydrase activities and renal electrol5fe excretion in rats. Am J Physiol 184 83-90. 

Archibald in the case of dog kidney glutaminase, and by Greenstein and Leuthardt in the case of rat kidney. Errera was able to show that in rat liver the phosphate-activated glutaminase (referred to as glutaminase I) was associated with the insoluble particles—an observation later confirmed by Shepherd and Kalnitsky, who established that this glutaminase activity was largely associated with, and bound to, the mitochondrial fraction. The purification of animal glutaminases beyond 3- to 4-fold has not as yet been realized, and thus an adequate explanation of the effect of anions and other factors is difficult. 

Figure 8.29 The initial reactions of glutamine metabolism in kidney, intestine and cells of the immune system. The initial reaction in all these tissues is the same, glutamine conversion to glutamate catalysed by glutaminase the next reactions are different depending on the function of the tissue or organ. In the kidney, glutamate dehydrogenase produces ammonia to buffer protons. In the intestine, the transamination produces alanine for release and then uptake and formation of glucose in the liver. In the immune cells, transamination produces aspartate which is essential for synthesis of pyrimidine nucleotides required for DNA synthesis otherwise it is released into the blood to be removed by the enterocytes in the small intestine or by cells in the liver.

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. 

In most terrestrial animals, glutamine in excess of that required for biosynthesis is transported in the blood to the intestine, liver, and kidneys for processing. In these tissues, the amide nitrogen is released as ammonium ion in the mitochondria, where the enzyme glutaminase converts glutamine to glutamate and NHj (Fig. 18-8). The NHj from intestine and kidney is transported in the... 

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. 

There the glutamine is sequentially deamidated by glutaminase and deaminated by kidney glutamate dehydrogenase. 

The kidney takes up glutamine, which is deaminated by glutaminase,... 

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. 

This amide of glutamic acid has properties similar to those of asparagine. The y-amido nitrogen, derived from ammonia, can be used in the synthesis of purine and pyrimidine nucleotides (Chapter 27), converted to urea in the liver (Chapter 17), or released as NH3 in the kidney tubular epithelial cells. The last reaction, catalyzed by the enzyme glutaminase, functions in acid-base regulation by neutralizing H+ ions in the urine (Chapter 39). 

Ammonia is produced by oxidative and nonoxidative deaminations catalyzed by glutaminase and glutamate dehydrogenase (Chapter 17). Ammonia is also released in the purine nucleotide cycle. This cycle is prominent in skeletal muscle and kidney. Aspartate formed via transamination donates its a-amino group in the formation of AMP the amino group is released as ammonia by the formation of IMP. 

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