Amino acids enzymes glutamine

The enzymic production of ammonia from amino acid amides is limited chiefly to the two naturally occurring amino acid amides, glutamine and asparagine. Reviews of various aspects of this subject have appeared (240, m). 

An alternative to modifying the functional group attached to fibrils is to utilise the chemistry present in the amino acid side chains. Furthermore, as peptides often undergo specific modification by enzymes in vivo, these could be harnessed for synthetic purposes. Qll (Ac-QQKFQFQFEQQ-Am, a fibril-forming peptide based on Pi 1-2), was coupled to lysine-based molecules by treatment with an enzyme (tissue transglutaminase, TGase) which results in a reaction between lysine and glutamine side chains [72] (Fig. 32). 

The enzymes glutamate dehydrogenase, glutamine synthetase, and aminotransferases occupy central positions in amino acid biosynthesis. The combined effect of... 

While ammonia, derived mainly from the a-amino nitrogen of amino acids, is highly toxic, tissues convert ammonia to the amide nitrogen of nontoxic glutamine. Subsequent deamination of glutamine in the liver releases ammonia, which is then converted to nontoxic urea. If liver function is compromised, as in cirrhosis or hepatitis, elevated blood ammonia levels generate clinical signs and symptoms. Rare metabolic disorders involve each of the five urea cycle enzymes. 

Histamine is synthesised by decarboxylation of histidine, its amino-acid precursor, by the specific enzyme histidine decarboxylase, which like glutaminic acid decarboxylase requires pyridoxal phosphate as co-factor. Histidine is a poor substrate for the L-amino-acid decarboxylase responsible for DA and NA synthesis. The synthesis of histamine in the brain can be increased by the administration of histidine, so its decarboxylase is presumably not saturated normally, but it can be inhibited by a fluoromethylhistidine. No high-affinity neuronal uptake has been demonstrated for histamine although after initial metabolism by histamine A-methyl transferase to 3-methylhistamine, it is deaminated by intraneuronal MAOb to 3-methylimidazole acetic acid (Fig. 13.4). A Ca +-dependent KCl-induced release of histamine has been demonstrated by microdialysis in the rat hypothalamus (Russell et al. 1990) but its overflow in some areas, such as the striatum, is neither increased by KCl nor reduced by tetradotoxin and probably comes from mast cells. 

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. 

Lysine is the most common site for N-methylation, but methylation can also occur on arginine, histidine, glutamine, and asparagine. The enzymes responsible for N-methylation are known as N-methyltransferases aided with SAM as a cosubstrate. All forms of methylation share the same mechanism the nucleophilic amino acid side chain attacks the electrophilic methyl group of SAM and releases S-adenosylhomocysteine (SAH) (Scheme 7). 

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. 

Many enzymes in the cell are organised into sequences, so that the reactions they catalyse are integrated into pathways or processes. In these pathways, a precursor or substrate is converted to a product, e.g. glucose is converted to lactic acid amino acids are polymerised to form protein glutamine is converted to aspartate. These pathways have both a thermodynamic and a kinetic structure. The thermodynamic structure is presented in Chapter 2. The kinetic structure is described here. There are three basic facts that must be appreciated before the kinetic structure is explained. 

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