Glutamate/glutamic acid synthase

In E. coli GTP cyclohydrolase catalyzes the conversion of GTP (33) into 7,8-dihydroneoptetin triphosphate (34) via a three-step sequence. Hydrolysis of the triphosphate group of (34) is achieved by a nonspecific pyrophosphatase to afford dihydroneopterin (35) (65). The free alcohol (36) is obtained by the removal of residual phosphate by an unknown phosphomonoesterase. The dihydroneoptetin undergoes a retro-aldol reaction with the elimination of a hydroxy acetaldehyde moiety. Addition of a pyrophosphate group affords hydroxymethyl-7,8-dihydroptetin pyrophosphate (37). Dihydropteroate synthase catalyzes the condensation of hydroxymethyl-7,8-dihydropteroate pyrophosphate with PABA to furnish 7,8-dihydropteroate (38). Finally, L-glutamic acid is condensed with 7,8-dihydropteroate in the presence of dihydrofolate synthetase. 

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... 

Among the numerous enzymes that utilize pyridoxal phosphate (PLP) as cofactor, the amino acid racemases, amino acid decarboxylases (e.g., aromatic amino acids, ornithine, glutamic acid), aminotransferases (y-aminobutyrate transaminase), and a-oxamine synthases, have been the main targets in the search for fluorinated mechanism-based inhibitors. Pharmaceutical companies have played a very active role in this promising research (control of the metabolism of amino acids and neuroamines is very important at the physiological level). 

ZD-9331 is a non-nucleosidic inhibitor of thymidylate synthase. It is also an antifolate, in which the quinazoline moiety replaces the pteridine entity, structurally close to methylene tetrahydrofolate (i.e., the second substrate of thymidylate synthase). Moreover, replacement of the acid function of glutamic acid by a tetrazole renders polyglutamination impossible. Consequently, ZD-9331 is active on tumors that are resistant to the usual antifolates. ... 

Nitric oxide (NO-) is generated enzymatically from glutamate by the nitric acid synthase and is responsible for a large number of diverse biological processes (for a review, see Nathan 1992 for spin trapping of the ensuing radicals, see Tsai et al. 2000). It was soon realized that an excess production of NO- is toxic, and a part of its toxicity was attributed to its reaction with 02-, i.e the formation of peroxynitrite [reactions (30) and (31)] (Beckman et al. 1990 for a review, see Murphy et al. 1998). 

Tho data in Table 9.1 are from an cxporlment involving foly] poly glutamate synthase. The enzyme was obtained in purified form from liver and was mixed with glutamic acid, ATP, and the indicated form of foiate. The mixture was incubated to permit the enzyme to catalyze the attachment of glutamafc residues to the folate. What do you think would be the effect of a vitamin Bij deficiency on the rate of polyglutamation of dietary folates, flint Dietary folates occur in the bloodstream initially as 5-melhyl-l UPteGtu, and enter the cell in this form. 

The figure shows the steps catalyzed by glutamine synthase and the structural similarity between glutamic acid, MSO, and glufosinate. 

Poly(ADP-ribose) synthase Glutamic acid y-COOH (histone HI), adenonsine ribose 2 -OH, and ... 

For the biosynthetic transfer of ammonia, the carboxylic acid function of glutamic acid is activated by ATP. In case phosphinothricin is present, this undergoes the same activation. The resulting phosphorylated phosphinothricin inhibits glutamine synthase in a competitive manner and functions as a substrate analogue- and transition state analogue-inhihitor. [13]... 

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