Tryptophan adenylate

The anticonvulsant properties of the drug would appear to be due to its ability to inhibit fast sodium channels, which may be unrelated to its psychotropic effects. Like lithium, it has been shown to decrease the release of noradrenaline and reduce noradrenaline-induced adenylate cyclase activity unlike lithium, it seems to have little effect on tryptophan or 5-HT levels in patients at therapeutically relevant concentrations. It also reduces dopamine turnover in manic patients and increases acetylcholine... 

Hermoni M, Lerer B, Ebstein RP, et al Chronic lithium prevents reserpine-induced supersensitivity of adenylate cyclase. J Pharm Pharmacol 32 510-511, 1980 Hertzman PA, Blevins WL, Mayer J, et al Association of the eosinophilia-myalgia syndrome with the ingestion of tryptophan [see comments]. N Engl J Med 322 869-873, 1990... 

Dimicoli, J. L. and Helene, C., Interactions of aromatic residues of proteins with nucleic acids. I. Proton magnetic resonance studies of the binding of tryptophan-containing peptides to poly(adenylic acid) and deoxyribonucleic acid, Biochemistry, 13(4], 714, 1974. 

Murty, C. N., Verney, E., and Sidransky, H., Effect of tryptophan on polyribo-adenylic acid and polyadenylic acid-messenger ribonucleic acid in rat liver, Lab. Invest., 34[1], 77, 1976. 

NaF is an inhibitor of glycolysis and negatively affects the adenylate cyclase system. Pretreatment (0.5 h) and posttreatment (1 h) with L-tryptophan before but not after NaF (1 to 2 h before kill) led to marked improvement of hepatic polyribosomal aggregation and protein synthesis.188... 

Figure 3 9 Biosynthesis of natural and unnatural cyclomarin and cyclomarazine analogs. Supplementing cultures of the S. arenicola cymD mutant with tryptophan analogs yields known and novel cyclomarins and cyclomarazines. Abbreviations A, adenylation domain C, condensation domain M1-M7, modules 1-7 MT, methyltransferase T, thiolation domain and TE, thioesterase.

M is synthesized from serotonin by acetylation to A-acetyl rotonin, followed by methylation (catalysed by acetylserotonin methyltransferase, EC 2.1.1.4) to M.In the pineal gland M. biosynthesisis is controlled by epinephrine, which stimulates adenylate t clase (EC 4.6.1.1), which in turn stimulates protein kinase. The first three steps of M. synthesis (L-tryptophan S-hydroxytryptophan -> serotonin - A-acetyl-5-hydroxytryptamine) are promoted in this way, but the methyltransferase is not affected. However, the rate-limiting step is catalysed by serotonin A-acetyltransferase. M. is inactivated and excreted as 6-hydroxymelatonin, or as 5-methoxyindole-acetic acid. 

Quinolinate decarboxylation and conversion to nicotinic acid mononucleotide is catalysed by quinolinate phosphoribosyltransferase, a rate-limiting enzyme in the conversion of tryptophan to NAD the reaction requires Mg and is negatively regulated by nicotinamide. Next the transfer of adenylate from ATP by an intermediate of nicotinamide/nicotinate-mononucleotide-adenyl-transferases isoenzymes (NMNAT, see below) yields nicotinic acid adenine... 

A transfer of the adenylyl group i.e., a P—0 split has not been obtained so far (or maybe has not been looked for) with the adenylates in the absence of enzyme. In the presence of the activating enzymes, on the other hand, the adenylyl group is veiy readily transferred onto pyrophosphate to give ATP 116, 169, 164, 177). This reaction, however, is not specific, since tryptophan activating enzyme, for example, can synthetize ATP from all the amino acid adenylates tested 116) as well as from the adenylate of D-tiyptophan 169). The same transfer of the AMP moiety onto PP does, of course, also occur in the amino acid catalyzed ATP-PP exchange reaction. 

The existence of an acyl-adenylate bound to enzyme has been demonstrated in the case of tryptophan activation (344). Tryptophan was incubated with ATP in the presence of substrate quantities of purified tryptophan-activating enzyme. Adenyl-tryptophan was isolated and chemically characterized after its removal from the denatured enzyme. 

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