Asparagine synthetase

Figure 28-4. The asparagine synthetase reaction. Note similarities to and differences from the glutamine synthetase reaction (Figure 28-2).

Figure 7 The direct and indirect pathways of tRNA asparaginylation. The direct pathway consists of charging by AsnRS on tRNA " of free Asn formed with asparagine synthetase A or B. The Asn-tRNA " binds the EF-Tu factor in bacteria (or EF-1A in eukaryotes and archaea) to be carried to the ribosome, in the indirect pathway, a nondiscriminating AspRS (ND-AspRS) charges Asp on tRNA " Asp-tRNA " does not bind the eiongation factor but is converted by the tRNA-dependent trimeric amidotransferase GatCAB into Asn-tRNA ", which binds the EF-Tu factor and is carried to the ribosome where it is used for polypeptide chain elongation.

A three-substrate, four-product enzyme reaction scheme in which the first two substrates bind in an ordered fashion followed by the release of the first product. The third substrate then binds and the remaining three products are released in order (thus, E + A EA is followed by EA + B (EAB FP) F -I- P and then F + C (EC EQRS) ERS + Q followed by ERS ES + R and ES E + S). There are indications that asparagine synthetase from certain sources may have this reaction scheme. 

ASPARAGINE SYNTHETASE CARNOSINE SYNTHETASE LEUCYL-tRNA SYNTHETASE... 

ASPARAGINE AMINOTRANSFERASE ASPARAGINE SYNTHETASE 1 -Aspartamido-j8-N-acetylglucosamine ami-dohydrolase,... 

ARACHIDONYL-CoA SYNTHETASE ARGININOSUCCINATE SYNTHETASE ASPARAGINE SYNTHETASE... 

The liberated NH3 can attack the (3-aspartyl-AMP as indicated in the accompanying diagram to form asparagine. However, it is also possible that NH3 is transferred via covalently bonded complexes99 and is never free NH3. An asparagine synthetase that utilizes free NH3 as a nitrogen donor is also present in many organisms. 

Many proteins have structures related to those of aminoacyl-tRNA synthetases.282 283 For example, asparagine synthetase A functions via an aspartyl-adenylate intermediate (Chapter 24, Section B), and its structure resembls that of aspartyl-tRNA synthetase.284 The his G gene of histidine biosynthesis (Fig. 25-13) encodes an ATP phosphoribosyltransferase with structural homology to the catalytic domain of histidyl-tRNA synthetase.284 The reason is not clear, but some aminoacyl-tRNA synthetases, especially the histidyl-tRNA synthetase, are common autoantigens for the inflammatory disease polymyosititis.285 286... 

Fig. 1.3 Reactions showing synthesis of glutamate in brain. Aspartate aminotransferase (1) glu-taminase (2) glutamate dehydrogenase (3) GABA aminotransferase (4) alanine aminotransferase (5) ornithine aminotransferase (6) Al-pyrroline 5-carboxylic acid dehydrogenase (7) and asparagine synthetase (8)...

Tumor cells can develop the potential to newly synthesize l-asparagine intra-p ] ii arjii which —the srilt resistant to the action of 1-ASP [9], hfschenisms that lead to derepression of die gene for asparagine synthetase have not yet been fully elucidated Some progress toward understanding these events comes from... 

A. Queen, S.. Gong, M. Rtmann, and C. Basilieo. Qguiizalion and expression of the cell cycle gene, till, that encodes asparagine synthetase Mo/. CelL BioL 92350 (1989). 

Romagni, J. G., Duke, S. O. and Dayan, F. E. 2000. Inhibition of plant asparagine synthetase by monoterpene cineoles. Plant Physiol. 123, 303-313... 

Normal cells have high levels of asparagine synthetase and are able to make sufficient asparagine for protein synthesis and cell growth... 

There are a number of allelochemicals among the mono-, sesqui-, and diterpenoids. In particular, plants in arid and semiarid regions produce diverse volatile terpenoids with allelopathic activity.5 Among the volatile monoterpenes, 1,8-cineole (4) and camphor (5) exhibit strong growth inhibitory effects on plants and are considered to be involved in plant competition. 1,4-Cineole (6), a minor isomer of 1,8-cineole, is a potent inhibitor of asparagine synthetase.6 -Menthane-3,8-diols (fir 7 and frw .r8), -menth-2-en-l-ols (cis 9 and trans 10), thymol (11), carvacrol (12), 1,8-cineole, cr-pinene (13), and /3-pinene (14) were isolated as allelopathic monoterpenes from Eucalyptus species.7 Eucalyptus trees also produce allelopathic sesquiterpenes including spathulenol (15), and a-, (3-, and 7-eudesmols (16-18).7... 

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