Glutamine enzymic

Both DON and azaserine show a mixed type of inhibition with glutamine enzymes. Because of the structural similarity between them and glutamine they compete for binding to the active site, however, once bound... 

Although the antibacterial and antifungal activities of bialaphos and phosphinothricin were not found to be usehil, the two agents were later used as biodegradeable, relatively nonselective, postemergent herbicides. Glutamine synthetase inhibition is toxic to plants because the enzyme is key to ammonia assimilation. There is some selectivity for individual plant species as shown by the LD for bialaphos ranging from 0.125 to 8.5 kg/ha (301—303). 

Both threo- (14) and eo f >"4-fluoro-DL-glutamic acid (/5) are noncompetitive inhibitors of glutamine synthase, an enzyme that catalyzes the synthesis of glutamine from L-glutamic acid and ammonia. This mhibibon may explain the... 

Many enzymes (see Chapters 14 to 16) derive at least some of their catalytic power from oligomeric associations of monomer subunits. This can happen in several ways. The monomer may not constitute a complete enzyme active site. Formation of the oligomer may bring ail the necessary catalytic groups together to form an active enzyme. For example, the active sites of bacterial glutamine synthetase are formed from pairs of adjacent subunits. The dissociated monomers are inactive. 

As mentioned in Section II., Meister and his co-workers (64) have studied extensively the substrate specificity of the enzyme glutamine synthetase from... 

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. 

Condensation of CO2, ammonia, and ATP to form carbamoyl phosphate is catalyzed by mitochondrial carbamoyl phosphate synthase I (reaction 1, Figure 29-9). A cytosolic form of this enzyme, carbamoyl phosphate synthase II, uses glutamine rather than ammonia as the nitrogen donor and functions in pyrimidine biosynthesis (see Chapter 34). Carbamoyl phosphate synthase I, the rate-hmiting enzyme of the urea cycle, is active only in the presence of its allosteric activator JV-acetylglutamate, which enhances the affinity of the synthase for ATP. Formation of carbamoyl phosphate requires 2 mol of ATP, one of which serves as a phosphate donor. Conversion of the second ATP to AMP and pyrophosphate, coupled to the hydrolysis of pyrophosphate to orthophosphate, provides the driving... 

Since biosynthesis of IMP consumes glycine, glutamine, tetrahydrofolate derivatives, aspartate, and ATP, it is advantageous to regulate purine biosynthesis. The major determinant of the rate of de novo purine nucleotide biosynthesis is the concentration of PRPP, whose pool size depends on its rates of synthesis, utilization, and degradation. The rate of PRPP synthesis depends on the availabihty of ribose 5-phosphate and on the activity of PRPP synthase, an enzyme sensitive to feedback inhibition by AMP, ADP, GMP, and GDP. 

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. 

The mutation of ThrlSl, Glyl82, or Glul83 to alanine, or of Glul83 to glutamine also completely inhibited the ATP or acetylphosphate-dependent Ca transport, without effect on the phosphorylation of the enzyme by ATP in the presence of Ca or by Pi in the absence of Ca [127]. The phosphoenzyme formed from ATP retained its ADP-sensitivity at low concentration and alkaline pH, but its rate of decomposition was much slower than that of the wild-type enzyme in the presence of EGTA. These observations implicate the 181-183 region in the conformational changes related to Ca translocation. 

---