Anthranilic acid tryptophan

The majority of alkaloids have been found to be derived from amino acids, such as tyrosine, phenylalanine, anthranilic acid, tryptophan/tryptamine, ornithine/arginine, lysine, histidine and nicotinic acid (Fig. 2.1). However, alkaloids maybe derived from other precursors such as purines in case of caffeine, terpenoids, which become aminated after the main skeleton has been synthesized i.e. aconitine or the steroidal alkaloids, are found in the Solanaceae and Liliaceae. Alkaloids may also be formed from acetate-derived polyketides, where the amino nitrogen is introduced as in the hemlock alkaloid, coniine. 

The biosynthesis and metabolism of nicotinic acid in disease has received little attention metabolic studies deal mainly with normal animals and man (01, R5). After a tryptophan load dose, the main catabolites in the urine are nicotinuric acid, N1-methylnicotinamide, nicotinamide, quinolinic acid, kynurenine, 6-pyridone, anthranilic acid, and 3-hydroxyanthranilic acid. These excretory products were estimated... 

The route of formation of the carbazole nucleus is still far from understood, and has been variously considered to arise from 3-prenylquinolone via a pathway involving shikimic acid (394) and mevalonic acid (MVA) (400) (Scheme 3.1) (1,112,362-366), anthranilic acid (397) and prephenic acid (404) via a pathway involving shikimic acid (394) (Scheme 3.2) (367), and also tryptophan (408) involving the mevalonate (400) pathway (Scheme 3.3) (133). All of these pathways lack experimental proof. However, based on the occurrence of the diverse carbazole alkaloids derived from anthranilic acid (397) in the family Rutaceae, the pathway... 

Alkaloids derived from L-tryptophan hold the indole nucleus in a ring system. The ring system originates in the shikimate secondary compounds building block and the anthranilic acid pathway. It is known that the shikimate block. 

Anthranilic acid (Figure 4.4) is an intermediate in the biosynthetic pathway to the indole-containing aromatic amino acid L-tryptophan (Figure 4.10). 

Anthranilic acid (Figure 6.106) is a key intermediate in the biosynthesis of L-tryptophan (see page 126) and so contributes to the elaboration... 

Streptonigrin.—Details of a study of the biosynthesis of streptonigrin (139) that had earlier been published in preliminary form (cf. Vol. 9, p. 24 Vol. 10, p. 23) are now available in full papers.51 52 In essence, the new results are that labelled anthranilic acid was not incorporated into streptonigrin (139),51 that l-rather than D-tryptophan was a precursor, and that label from C-7a in tryptophan (94) appeared, it was deduced, at C-8 in (139).52 The exclusive labelling of C-8 by tryptophan indicates that rings A and B do not derive from this amino-acid. These rings do not derive from phenylalanine and tyrosine, and negative results have been obtained with shikimic acid due, at the least, to poor cellular uptake.51... 

The emission peak at 500 nm was absent when the apoenzyme was excited at 290 nm47 (Fig. 9.11). This peak was also diminished in a mutant holoenzyme in which Trp-248 was replaced by phenylalanine.I8 It was proposed that this peak is due to energy transfer from the tryptophan residues to the coenzyme. Binding of anthranilic acid or alanine quenches the 500-nm peak and, therefore, interferes with the energy transfer.43 ... 

Preliminary results99 indicated that 11-demethyltomaymycin (118) had a similar genesis to anthramycin (116) from tryptophan and tyrosine, and these results have now been published in full.100 Tryptophan has been shown to provide ring A, presumably by catabolism through anthranilic acid. The results99,100 are summarized in Scheme 12. It is to be noted that methionine provides only the aromatic O-methyl group [in anthramycin there is an extra carbon present in the unit related to (119) which derives from methionine see above]. Further evidence from incorporation of labelled tyrosine indicates that the C7 unit (119) derives from seven tyrosine carbon atoms. The incorporation of L-[l-14C,2,3-3H2]tyrosine (tritium distribution H-2, 50% H-3-pro-S, 41.5% H-3-pro-R, 8.5%) with loss of half the tritium label was interpreted reasonably as involving loss only of the C-2... 

For the aromatic pathway (Figure 30.20), the critical control points are the condensation of phosphoenolpyruvate and erythrose-4-phosphate to 3-deoxy-D-arabinoheptulosonate 7-phosphate, DAHP, by DAHP synthase. For tryptophan, the formation of anthranilic acid from chorismic acid by anthranilate synthase is the second critical control point. The transcriptional regulation was overcome through the use of alternative promoters and allosteric regulation was circumvented by the classical technique of selection for feedback-resistant mutants using toxic analogues of the repressing compounds. 

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