Muscle glutamine

Figure 8.24 Some fates of glutamine that is released by muscle. Glutamine is released from the store of glutamine in the muscle but, for immune system and bone marrow, it may also be provided from adipocytes (Chapter 17). It is assumed that glutamine is present as a free amino acid in muscle and that there is a specific transport protein in the plasma membrane that can be regulated.

A. Alanine and glutamine are the major amino adds released from muscle. Glutamine is further metabolized in the gut and the kidney. Alanine is the major amino add that is converted to glucose in the liver. 

In muscle, glutamine synthetase is very active, catalyzing the formation of glutamine from glutamate and ammonia at the expense of a molecule of ATP. In the liver, the rate... 

Biolo G, Fleming RY, Maggi SP, et al. Inhibition of muscle glutamine formation in hyper-... 

Glutamine accounts for more than half of the total intramuscular free amino acid pool, making it one of the most abundant and versatile amino acids in the plasma and skeletal muscle. Glutamine is predominantly synthesized and stored in the skeletal muscle by the action of the enzyme glutamine synthetase. Adipose tissue, lungs, hver, and brain are also sites of synthesis of 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). 

The 2-oxoglutarate produced is recycled for transamination or may enter the TCA cycle. The ammonia liberated by oxidative deamination is used to form glutamine (from glutamate, catalysed by glutamine synthase) prior to export from the muscle cell ... 

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. 

Tissue electrodes [2, 3, 4, 5, 45,57], In these biosensors, a thin layer of tissue is attached to the internal sensor. The enzymic reactions taking place in the tissue liberate products sensed by the internal sensor. In the glutamine electrode [5, 45], a thick layer (about 0.05 mm) of porcine liver is used and in the adenosine-5 -monophosphate electrode [4], a layer of rabbit muscle tissue. In both cases, the ammonia gas probe is the indicator electrode. Various types of enzyme, bacterial and tissue electrodes were compared [2]. In an adenosine electrode a mixture of cells obtained from the outer (mucosal) side of a mouse small intestine was used [3j. The stability of all these electrodes increases in the presence of sodium azide in the solution that prevents bacterial decomposition of the tissue. In an electrode specific for the antidiuretic hormone [57], toad bladder is placed over the membrane of a sodium-sensitive glass electrode. In the presence of the antidiuretic hormone, sodium ions are transported through the bladder and the sodium electrode response depends on the hormone concentration. 

Glutamine is found in all cells in a combined form in peptides or proteins, but also in a free form. The highest free concentration of glutamine is found in muscle, where it acts as a store for use by other tissues. In fact, the total amount in all the skeletal muscle in the body is about 80 g, which is synthesised in the muscle from glucose and branched-chain amino acids (see Chapter 8). As with glycogen in the liver and triacylglycerol in adipose tissue. 

The content of glutamine in muscle is measured in a similar manner to that of glycogen. A biopsy of muscle is taken, extracted and the glutamine content measured by enzymes or by high pressure liquid chromatography (Appendix 2.1). 

Hormones can modify the concentration of precursors, particularly the lipolytic hormones (growth hormone, glucagon, adrenaline) and cortisol. The lipolytic hormones stimulate lipolysis in adipose tissue so that they increase glycerol release and the glycerol is then available for gluconeogenesis. Cortisol increases protein degradation in muscle, which increases the release of amino acids (especially glutamine and alanine) from muscle (Chapter 18). 

In muscle, the concentrations of alanine, aspartate, glutamate, glutamine, leucine, serine and valine are high that of glutamine is the highest (c. 20mmol/L). The lowest are those of methionine, tryptophan and tyrosine. 

The major role of skeletal muscle is movement, which is described and discussed in Chapter 13). Nevertheless, since muscle comprises 40% of the body it is large enough to play a part in control of the blood concentrations of the major fuels glucose, fatty acids, triacylglycerol and some amino acids. Skeletal muscle contains the largest quantity of protein in the body, which is used as a source of amino acids under various conditions (e.g. starvation, trauma, cancer see above). It plays an important part in the metabolism, in particular, of branched-chain amino acids, glutamine and alanine, which are important in the overall metabolism of amino acids in the body (discussed below). 

Figure 8.17 The metabolism of branched-chain amino acids in muscle and the fate of the nitrogen and oxoacids. The a-NH2 group is transferred to form glutamate which is then aminated to form glutamine. The ammonia required for aminab on arises from glutamate via glutamate dehydrogenase, but originally from the transamination of the branded chain amino acids. Hence, they provide both nitrogen atoms for glutamine formation.

The concentration difference is that between blood in the femoral artery and that in the femoral vein. The minus sign indicates release from the muscle. Data taken from Felig (1975). It is estimated that about 80 g of glutamine is released each day from skeletal muscle. 

Figure 8.23 Formation of glutamine from glucose and branched-chain amino adds in muscle and adipose tissue and probably in the lung. Oxoacids may also be released into blood for oxidation in the liver.

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. 

Glutamine is stored in muscle approximately 80 g in the total skeletal muscle in the body. This is an amount similar to that of glucose which is stored as glycogen in the liver (Chapters 2 and 6). 

Figure 8.31 Comparison of glutamine as a fuel in the blood with glucose and fatty acids. The concentration of glutamine in the blood is similar to that of fatty acid. The amount of glutamine stored in muscle is similar to the amount of glycogen stored in the liver that is, about 80 g. Mobilisation of each of these stored fuels is discussed in Chapters 6, 7, 17 and 18. It appears that glutamine is stored free in the cytosol. Polyglutamine on vesicles containing glutamine have not been found.

The long tail of myosin contains a high proportion of the amino acids leucine, isoleucine, aspartate and glutamate. These are released upon the degradation of myosin by intracellular proteases and peptidases and they provide nitrogen for the synthesis of glutamine. It is then stored in muscle and is a very important fuel for immune cells (Chapter 17). 

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