Kidney glutamine

Major amino acids emanating from muscle are alanine (destined mainly for gluconeogenesis in liver and forming part of the glucose-alanine cycle) and glutamine (destined mainly for the gut and kidneys). 

Glutamine is exported from the muscle and extracted from blood mainly by the kidneys or the gut hepatic uptake of glutamine is relatively low in comparison. In the renal tubular cells, glutamine is deaminated in the processes of urinary acidification (see Figure 8.11) or used by the intestinal cells as a fuel. 

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. 

Gluconeogenesis. The gluconeogenic pathway is present in the kidney, as in the liver. Thus, amino acids (and lactate) can be converted to glucose in the kidney but a major precursor, in acidotic conditions, is glutamine. 

In addition to synthesis, mnscle also stores glntamine. It is estimated that the total qnantity stored in aU the skeletal mnscles is about 80 g. The glutamine released by muscle can be utilised by the kidney, enterocytes in the small intestine, colonocytes, aU the immune cells and the cells in the bone marrow (Figure 8.24). Details of the pathways of utilisation by these tissues are discussed. 

The major tissues that use glutamine are kidney, small intestine, colon, immune cells and bone marrow cells. Rates of utilisation by these last four tissues cannot be measured in vivo. Rates of utilisation by isolated cells have been measured in vitro (Chapters 17 and 21). 

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.

Comparison of the early stages of glutamine metabolism in kidney, intestine and lymphocytes... 

Kidney uses glutamine in acidosis to provide ammonia, but the oxoglutarate that is produced, is oxidised to generate ATP. 

The anorexia suffered by cancer patients is likely to arise from a combination of psychological stress, altered senses of taste and smell and increased levels of cytokines, which influence the appetite and satiety centres in the hypothalamus. There are several consequences micronutrient intake will be diminished and this may contribute to the signs and symptoms of the disease. Plasma amino acid levels will fall, as in starvation (Chapter 16). Synthesis of glutamine (by muscle, adipose and lung), aspartate (by liver), glutathione (by the intestine) and arginine (by the kidney) will all be compromised. The metabolic significance of all of these is discussed in Chapter 18. 

The skeletal muscle is the most important site for degradation of the branched-chain amino acids (Val, Leu, lie see p. 414), but other amino acids are also broken down in the muscles. Alanine and glutamine are resynthesized from the components and released into the blood. They transport the nitrogen that arises during amino acid breakdown to the liver (alanine cycle see above) and to the kidneys (see p. 328). 

Jones TW, Chen Q, Schaeffer V, et al. 1988. Immunohistochemical localization of glutamine transaminase K, a rat kidney cysteine conjugate p-lyase, and the relationship to the segment specificity of cysteine conjugate nephrotoxicity. Mai Pharm 34 621-627. 

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... 

Tin metabolic acidosis (p. 652) there is an increase in glutamine processing by the kidneys. Not all the excess NH4 thus produced is released into the bloodstream or converted to urea some is excreted directly into the urine. In the kidney, the NH% forms salts with metabolic acids, facilitating their removal in the urine. Bicarbonate produced by the decarboxylation of a-lcetoglutarate in the citric acid cycle can also serve as a buffer in blood plasma. Taken together, these effects of glutamine metabolism in the kidney tend to counteract acidosis. ... 

The ability of enzyme preparations from various animal tissues to catalyze transfer of the glutamyl unit from glutamine or glutathione to certain a-amino acids and peptides, first observed by Hanes et al. (38), has been examined in several laboratories (32, 35, 39-41). Enzymes of this type have been studied recently by Orlowski and Meister (in hog kidney) (32) and by Szewczuk and Baranowski (in beef kidney) (41)-Results with the hog kidney enzyme will be reviewed here the beef enzyme is quite similar in many respects, but it is not identical in physical properties. 

Kidney-Cortex (S2,3) Alanine, glutamine, valine, glucose, lactate, and 3-hydroxybutyrate Creatinine... 

Each tissue, including the bloodstream, has a free amino acid pool. This amounts to a total of about 100 g. By far the largest fraction, 50-80%, is located in muscle. Kidney accounts for about 4%, liver for 10%, and the bloodstream another 4%. Glutamine and glutamate are major components of such pools. Free amino acid pools are in equilibrium with tissue protein. Tissue proteins are in a constant state of turnover, that is, biosynthesis and degradation from and to free amino acids. Only plasma proteins, which are largely synthesized in the liver, are not in equilibrium with the plasma free amino acid pool. 

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