Guanylate synthetase mechanism

Increased enzyme activity may be due to increased concentrations of nucleotide substrates, or by other mechanisms. For example, GTP is required as a substrate for adenylosuccinate synthetase, and ATP is required for guanylate synthetase in addition, ATP activates adenylate deaminase (33). 

The supply of nonnucleotide substrates may also be an important control mechanism for these pathways. In Ehrlich ascites tumor cells aspartate concentrations were found to be rate-limiting for adenylate synthesis from hypoxanthine (46), and glutamine levels limited guanylate synthetase activities in these cells and in erythrocytes (47)-... 

The glutamine analogue, diazo-oxo-norleucine, and the aspartate analogue, hadacidin (iV-formyl hydroxyaminoacetic acid), inhibit guanylate synthetase and adenylosuccinate synthetase, respectively. Alanosine (2-amino-3-nitrohydroxylaminopropionic acid) is also an inhibitor of adenylate synthesis from inosinate, but its mechanism of inhibition is not yet clear (52). 

The enzyme catalyzing the amidation of the nicotinic acid- DPN to the active coenzyme has been detignated DPN synthetase q. (3c)]. The mechanism of the reaction is timilar to that involved in the formation of guanylic acid 13S, 1S4) as well as a-N-formylglycinamide in which the glutamine nitrogen is transferred to the acid yielding the amide 133). At present, there is no explanation of the reason for the ATP requirement in the reaction. 

---