Amino acid metabolism glutamine

Excretion into urine of ammonia produced by renal mbu-lar cells facilitates cation conservation and regulation of acid-base balance. Ammonia production from intracellular renal amino acids, especially glutamine, increases in metabolic acidosis and decreases in metabolic alkalosis. 

Connections To amino acid metabolism by the requirement for glutamine and aspartate. 

In earlier studies the in vitro transition metal-catalyzed oxidation of proteins and the interaction of proteins with free radicals have been studied. In 1983, Levine [1] showed that the oxidative inactivation of enzymes and the oxidative modification of proteins resulted in the formation of protein carbonyl derivatives. These derivatives easily react with dinitrophenyl-hydrazine (DNPH) to form protein hydrazones, which were used for the detection of protein carbonyl content. Using this method and spin-trapping with PBN, it has been demonstrated [2,3] that protein oxidation and inactivation of glutamine synthetase (a key enzyme in the regulation of amino acid metabolism and the brain L-glutamate and y-aminobutyric acid levels) were sharply enhanced during ischemia- and reperfusion-induced injury in gerbil brain. 

Figure 21.24 An overview of amino acid metabolism, particularly amino acid metabolism, in a patient suffering from cancer. The tumour acts as a sink for glucose, amino acids and glutamine. As tumour grows in size, the sink is exaggerated and cachexia develops. This diagram can be considered with that in Figure 21.22 in order to include fatty acids in tumour metabolism. Note the thicker line to indicate magnitude of release of glutamine by muscle.

Vinblastine suppresses cell growth during metaphase, affects amino acid metabolism, in particular at the level of including glutamine acid into the citric acid cycle and preventing it from transformation into urea, and it also inhibits protein and nucleic acid synthesis. 

Glutamine synthetase is found in all organisms. In addition to its importance for NHj assimilation in bacteria, it has a central role in amino acid metabolism in mammals, converting toxic free NHj to glutamine for transport in the blood (Chapter 18). 

The protein and amino-acid metabolism of the liver is characterized by three essential functions (1.) production and breakdown of proteins, (2.) production and breakdown of amino acids as well as regulation of their concentrations in the blood, and (i.) detoxification of ammonium via the synthesis of urea (= excretory form) and glutamine (= non-toxic transport or storage form) with simultaneous regulation of the acid-base balance. The breakdown of branched-chain amino acids occurs only in the musculature by way of deamination, (s. pp 38, 43)... 

Two types of reactions play prominent roles in amino acid metabolism. In transamination reactions, new amino acids are produced when a-amino groups are transferred from donor a-amino acids to acceptor a-keto acids. Because transamination reactions are reversible, they play an important role in both amino acid synthesis and degradation. Ammonium ions or the amide nitrogen of glutamine can also be directly incorporated into amino acids and eventually other metabolites. 

The amino acids glutamine and glutamate are central to amino acid metabolism. Explain. 

Glutamate is a central amino acid in general amino-acid metabolism. It plays a major role in transamination, ammonia production, formation of ornithine, proline, glutamine, and g-amino butyric acid (GABA). 

Cumulative feedback Inhibition - Eight specific feedback inhibitors, which are either metabolic end products of glutamine (tryptophan, histidine, glucosamine-6-phosphate, carbamoyl phosphate, CTP, or AMP) or indicators of the general status of amino acid metabolism (alanine or glycine), can bind to any of the subunits of the enzyme and at least partially inhibit it. The more inhibitors that bind, the greater the inhibition. 

See also Table 5.1, Amino Acids, Genetic Code, Y-Carboxyglutamic Acid, Glutamine, Glutamate as a Precursor of Other Amino Acids (from Chapter 21), Transamination in Amino Acid Metabolism (from Chapter 20), Citric Acid Cycle Intermediates in Amino Acid Metabolism (from Chapter 21), Essential Amino Acids... 

The liver is the major site of amino acid metabolism in the body and the major site of urea synthesis The liver is also the major site of amino acid degradation. Hepatocytes partially oxidize most amino acids, converting the carbon skeleton to glucose, ketone bodies, or CO2. Because ammonia is toxic, the liver converts most of the nitrogen from amino acid degradation to urea, which is excreted in the urine. The nitrogen derived from amino acid catabolism in other tissues is transported to the liver as alanine or glutamine and converted to urea. 

Fig. 42.13. Amino acid metabolism in the gut. The pathways of glutamine metabolism in the gut are the same whether it is supplied by the diet (postprandial state) or from the blood (postabsorptive state). Cells of the gut also metabolize aspartate, glutamate, and BCAA. Glucose is converted principally to the carbon skeleton of alanine. a-KG = a-ketoglutarate GDH = glutamate dehydrogenase TA = transaminase.

The liver is the major site of amino acid metabolism. It is the major site of amino acid catabolism and converts most of the carbon in amino acids to intermediates of the TCA cycle or the glycolytic pathway (which can be converted to glncose or oxidized to CO2), or to acetyl CoA and ketone bodies. The fiver is also the major site for urea synthesis. It can take up both glutamine and alanine and convert the... 

In these hypercatabolic states, skeletal muscle protein synthesis decreases, and protein degradation increases. Oxidation of BCAA is increased and glutamine production enhanced. Amino acid uptake is diminished. Cortisol is the major hormonal mediator of these responses, although certain cytokines may also have direct effects on skeletal muscle metabohsm. As occurs during fasting and metabolic acidosis, increased levels of cortisol stimulate ubiquitin-mediated proteolysis, induce the synthesis of glutamine synthetase, and enhance release of amino acids and glutamine from the muscle cells. 

Glycine, alanine, and serine are key indicators of amino acid metabolism in the ceU. Each of the other six compounds represents an end product of a biosynthetic pathway that depends on glutamine. Feedback inhibition is very effective because a single product molecule can inhibit an enzyme capable of synthesizing many hundreds or thousands of product molecules. 

The 5 phosphoribosyl-l-pyrophosphate required for purine synthesis is obtained from ATP and ribose-5-phosphate by reaction (11.39). Glutamine, which is also required, is obtained from glutamic acid by reaction (11.44), and the latter is obtained from a - oxoglutaric acid by reaction (11.124). The last reaction links the Krebs cycle with amino acid metabolism. 

Several laboratories have been concerned with the effect of ascorbic acid deficiency on amino acid metabolism. Two main aspects have been investigated (1) a rather unspecific effect on the amino acid content in muscle and in blood and (2) a more specific action of vitamin C on the hydroxylation of some amino acids or intermediates in amino acid biosynthesis. Vitamin C deficiency alters the ratio of the various amino acid concentrations in muscle and blood. In muscle, while glutamic acid, leucine, valine, and methionine levels increase, glutamine and aspartic acid concentrations decrease. In blood of scorbutic guinea pigs, the concentrations of most of the amino acids decrease, while phenylalanine, leucine, and histidine levels rise. There is no definite explanation for these changes they indicate only that ascorbic acid is directly or indirectly involved with amino acid metabolism. 

However, almost none of appropriate enzyme models have ever been reported for the reaction path control or the allosteric control in homogeneous aqueous solution(2). In biological systems, both control mechanisms are very frequently and significantly operating as in the case of the reaction path control of the amino acid metabolism by individual enzyme(3) or the allosteric control of levels of many important compounds by glutamine synthetase. 

Glutamine synthase catalyzes the reductive amina-tion ofa-ketoglutarateto give glutamate, a step in amino acid metabolism. 

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