Indole-3-pyruvic acid pathway

In a group of bacteria tryptophan degradation follows another pathway and yields indole, pyruvic acid and ammonia (Fig. 245). 

In addition to the pathway just outlined, tryptophan can result from the transamination of indole-pyruvic acid, but it seems unlikely that this reaction makes any important contribution to the biosynthesis. A trypto-phan-kynurenine-anthranilate-indole-tryptophan cycle has also been proposed i.e. the reverse of the catabolic pathway described in Fig. 58. However this sequence of reactions is only traversed if an excess of tryptophan is present and its function appears to be purely degradative. 

Overall, the biosynthesis of 160 is characterized by the dimerization of 168 to give the central structure of the molecule. This head-to-tail dimerization strategy is efficient, using the same substrate twice, and is a sensible route, given the existence of the shikimate pathway, which provides, in turn, a precursor to 168. An analogous dimerization route can be seen for the biosynthesis of K252c (1), described in Sect. 5, where two molecules of indole-3-pyruvic acid imine (125), derived in turn from L-tryptophan (123), are dimerized to give an intermediate that leads to chromopyrrolic acid (128). In both cases, the monomer precursors, either 168 or 125, serve as both nucleophiles and electrophiles, and are activated to react by the presence of the appropriate enzymes. 

INDOLMYCIN (20) is formed from pyruvate, and two enzymes active in initial stages of Its biosynthesis have been studied. They are a transaminase and aC-methyltransferase. The hypothetical route to indolmycin is by indole pyruvate, 3-methyl-indolepyruvate, indolmycenic acid (reduced alpha oxo group) and finally indolmycin which probably takes its amidine group from an arginine molecule 79. The closely related [pyrrolo (1,4) benzodiazepines] 80>81,82 antitumor antibiotics, anthramycin, tomaymycin and sibiromycin are formed from tryptophan (via the kynurenine pathway ), tyrosine and methionine-derived methyl groups 80.si.sz. 

Figure 5.42 Proposed tryptophan-dependent indole acetic acid biosynthesis pathways for Arabidopsis. Dashed arrows indicate that neither a gene nor enzyme activity has been identified in Arabidopsis. lAM, indole-3-acetamide IPA, indole-3-pyruvic acid lAAld, indole-3-acetaldehyde lAOx, indole-3-acetaldoxime 5-lAH-L-cys,...

Tryptophan is metabolized by several different pathways (Fig. 1) each yielding biologically important substances such as tryptamine and in particular serotonin (5-hydroxytryptamine), which seems to be involved in certain mental disorders. Indole-3-acetic acid is a plant growth hormone its precursor is tryptamine or indole-3-pyruvic acid. In humans, the microorganisms of the large intestine can further degrade indole-3-acetic acid to yield indole, skatole (3-methyl-indole) and other substances. 

Most known thiamin diphosphate-dependent reactions (Table 14-2) can be derived from the five halfreactions, a through e, shown in Fig. 14-3. Each half-reaction is an a cleavage which leads to a thiamin- bound enamine (center. Fig. 14-3) The decarboxylation of an a-oxo acid to an aldehyde is represented by step h followed by fl in reverse. The most studied enzyme catalyzing a reaction of this type is yeast pyruvate decarboxylase, an enzyme essential to alcoholic fermentation (Fig. 10-3). There are two 250-kDa isoenzyme forms, one an tetramer and one with an (aP)2 quaternary structure. The isolation of a-hydroxyethylthiamin diphosphate from reaction mixtures of this enzyme with pyruvate provided important verification of the mechanisms of Eqs. 14-14,14-15. Other decarboxylases produce aldehydes in specialized metabolic pathways indolepyruvate decarboxylase in the biosynthesis of the plant hormone indole-3-acetate and ben-zoylformate decarboxylase in the mandelate pathway of bacterial metabolism (Chapter 25). Formation of a-ketols from a-oxo acids also starts with step h of Fig. 14-3 but is followed by condensation with another carbonyl compound in step c, in reverse. An example is decarboxylation of pyruvate and condensation of the resulting active acetaldehyde with a second pyruvate molecule to give l -a-acetolactate, a reaction catalyzed by acetohydroxy acid synthase (acetolactate synthase). Acetolactate is the precursor to valine and leucine. A similar ketol condensation, which is catalyzed by the same S5mthase, is... 

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