Adenylate, synthesis

Dukhovich A, Sillero A, Sillero MA. Time course of luciferyl adenylate synthesis in the firefly luciferase reaction. FEBS Lett 1996 395 188-90. 

One striking feature of the two biosynthetic pathways leading from IMP is the requirement for ATP as a cofactor in guanylate synthesis and the reciprocal requirement for GTP as a cofactor in adenylate synthesis. This phenomenon has long been suggested as one mechanism by which the appropriate ATP/GTP ratio is maintained (83). 

It was not until 1953 that Goldwasser (9) and Williams and Buchanan (10) showed that purine bases could be converted to ribonucleotides by a one-step process, without the intermediate formation of ribonucleosides. The source of the ribose phosphate moiety was discovered in 1955 to be PP-ribose-P in the course of studies of adenylate synthesis by Kornberg et al. 11), and of inosinate synthesis by Korn et al. 12) extracts of yeast, beef liver, and pigeon liver were employed. The enzymes involved were at first called nucleotide pyrophosphorylases, but are now known as purine phosphoribosyltransferases. The general reaction is... 

The conversion of adenine to guanylate does not involve the reversal of the steps leading from inosinate to adenylate, for these reactions strongly favor adenylate synthesis. However, mutants blocked in one of these... 

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). 

Hadacidin, bredinin and mycophenolic acid, each shown to effect specific purine enzymes in other types of cells acted predictably to disrupt purine nucleotide synthesis by PRBC. The lack of a detectable effect on adenylate synthesis by alanosine may be due to an inability to form the active metabolite, L-alanosyl-AICOR, which requires an active de novo purine pathway (10). 

Y Xu, D Beckett. Biotinyl-5 -adenylate synthesis catalyzed by E. coli repressor of biotin biosynthesis. Methods Enzymol 279 405-421, 1997. 

Rhodes, W. C., and McElroy, W. D. (1958). The synthesis and function of luciferyl-adenylate and oxyluciferyl-adenylate. J. Biol. Chem. 233 1528-1537. 

Llamas A, RR Mendel, G Schwarz (2004) Synthesis of adenylated molybdopterin. An essential step for molybdenum insertion. J Biol Chem 279 55241-55246. 

This transmembrane signaling system involves a complex consisting of several functional proteins (Figure 7) stimulatory (e.g. P-adrenergic, dopamine Dp serotonin, vasopressin) [124] and inhibitory (e.g. a2-adrenergic, dopamine D2, opiod, and muscarinic) [125] receptors, stimulatory (Gs) and inhibitory (G ) G-proteins, and the catalytic protein, adenylate cyclase. On stimulation of a receptor, an associated G-protein binds GTP and the resulting receptor/G-protein/GTP complex then activates, or inhibits, adenylate cyclase in the catalysis of the synthesis... 

Li+ also inhibits several hormone-stimulated adenylate cyclases which, in some cases, appear to be related to side effects of Li+ therapy. For instance, Li+ inhibits the hydro-osmotic action of vasopressin, the antidiuretic hormone which increases water resorption in the kidney [136]. This effect is associated with polyuria, a relatively harmless side effect sometimes experienced with Li+ treatment, which arises from the inability of the kidney to concentrate urine. Li+ has been shown to inhibit vasopressin-stimulated adenylate cyclase activity in renal epithelial cells. Additionally, Li+ is reported to enhance the vasopressin-induced synthesis of prostaglandin E2 (PGE2) in vitro in kidney. PGE2 inhibits adenylate cyclase activity by stimulation of Gj, and, therefore, this effect may contribute to the Li+-induced polyuria. 

Li+ causes malformation and affects regeneration in some protozoans, for example Tetrahymenapyriformis [231], by inhibiting both DNA and RNA synthesis by affecting regeneration in Hydra [232], planarians [233], and annelids [234] and by affecting cell signaling mediated by both inositol phosphate metabolism [235] and adenylate cyclase [236] in slime molds. 

Adenosine triphosphate (ATP) is one of the most important cofactors involved in many of the synthetic reactions going on within the cell. Its recent large scale in vitro enzymatic synthesis from adenosine and acetylphosphate is of particular interest. Three enzymes immobilized in polyacrylamide gel were used adenosine kinase, adenylate kinase and acetate kinase (lip. ... 

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