By Edited by: Daniel L. Purich, Daniel L. Purich
This booklet is a component A in a subseries entitled "Amino Acid Metabolism". subject matters partially A can be of speedy curiosity to those that are greatly taken with amino acid assimilation and metabolism. Investigators drawn to enzyme mechanism and legislation also will locate this quantity particularly necessary.
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Additional info for Amino Acid Metabolism, Part A, Volume 72, Advances in Enzymology and Related Areas of Molecular Biology
Beyond the availability of substrates, the National Institutes of Health (NIH) group led by Stadtman identified that a hierarchy of metabolic con- ADVANCES IN THE ENZYMOLOGY OF GLUTAMINE SYNTHESIS 31 trol is at play, including (a) the covalent interconversion by a multistep adenylylatioddeadenylylation and uridylation/deuridylation cascade involving positive and negative effector control by metabolites whose concentrations depend on the availability of glutamine and ammonium ion; (b) the cumulative feedback inhibition by endproducts of glutamine-dependent biosynthetic pathways; (c) the catalytic and structural sites for divalent metal ions; and (d) metaboliteregulated repression of glutamine synthetase gene expression.
Thus, glutamine supply to these organs and the activity of the Na+coupled transporter N are major determinants of cell hydration, and glutamine can trigger a variety of effects on hepatic metabolism and gene expression simply by increasing hepatocellular hydration. Consequently, the role of the Na+-dependent transport system N is more than simply amino acid translocation across the plasma membrane. The transporter also acts as a transmembrane signaling system that modifies cell function in response to glutamine delivery by altering cell hydration (Haussinger and Lang, 1991).
The exchange catalyzed by the E. coli enzyme with glutamate occurs in the absence of ammonia and is partially inhibited by added ammonium chloride, as would be expected if the exchange reflects the mechanistic pathway for glutamine synthesis. Their positional isotope exchange results provided compelling kinetic evidence for a two-step mechanism wherein phosphoryl transfer from ATP to glutamate to form the acyl-P intermediate precedes reaction with ammonia. K. REGULATION OF BACTERIAL GLUTAMINE SYNTHETASE The de novo synthesis of nitrogen-containing metabolites involves glutamine as an amide nitrogen donor.