Indole metabolism

Another control effect may occur in the metabolic sequence leading from L-tryptophan to lAA. Natural phenolic growth inhibitors were checked for their influence on indole metabolism in the plants from which they were isolated, and were found to change the incorporation pattern of the radioactive precursor (Table 3) Although growth promotion and inhibition by phenols could thus partially be explained by the action of phenols on lAA biosynthesis, an effect on lAA destruction also seems feasible(3). 

It is often assumed that the accumulation of the amino acid or its derivatives interferes with important metabolic acitivites in the nervous system. At least four different theories have been proposed. The first postulates that phenylalanine metabolism directly affects the molecular system responsible for the maintenance of normal mental performance. However, one should not eliminate the possibility of an indirect effect by which the phenylalanine metabolites interfere with biochemical conversions in other pathways, thereby causing mental deficiency. An example of such an indirect mechanism is the chain reaction that links the distortion of phenylalanine metabolism to that of indole metabolism. Low serotonin levels in phenylke-tonurics could also cause mental retardation, but there is no correlation between serotonin levels and severity of mental retardation. Moreover, the role of serotonin in mental functions is not known. 

Functional gastrointestinal disturbances with alterations in the indole metabolism... 

Sjoerdsma, a. and Udenfriend, S., Studies on indole metabolism in patients with malignant carcinoid (argentatfinoma), J, Clin. Invest. 34, 914 (1955). 

The synthesis and metabolism of trace amines and monoamine neurotransmitters largely overlap [1]. The trace amines PEA, TYR and TRP are synthesized in neurons by decarboxylation of precursor amino acids through the enzyme aromatic amino acid decarboxylase (AADC). OCT is derived from TYR. by involvement of the enzyme dopamine (3-hydroxylase (Fig. 1 DBH). The catabolism of trace amines occurs in both glia and neurons and is predominantly mediated by monoamine oxidases (MAO-A and -B). While TYR., TRP and OCT show approximately equal affinities toward MAO-A and MAO-B, PEA serves as preferred substrate for MAO-B. The metabolites phenylacetic acid (PEA), hydroxyphenylacetic acid (TYR.), hydroxymandelic acid (OCT), and indole-3-acetic (TRP) are believed to be pharmacologically inactive. 

HT is metabolised primarily by MAO to 5-hydroxyindoleacetic acid (5-HIAA) (Fig. 9.4). In vitro, 5-HT is the preferred substrate for the MAOa, rather than the MAOb isoenzyme (see Chapter 8) and this appears to be the case in vivo since MAOa, but not MAOb, knock-out mice have increased concentrations of 5-HT in the brain. Obviously, because of its indole nucleus, 5-HT is not a substrate for the enzyme COMT which metabolises the catechol derivatives, dopamine and noradrenaline. However, other metabolic products of 5-HT are theoretically possible and one, 5-hydroxytryptophol,... 

Allen CC, DR Boyd, Ml Larkin, KA Reid, ND Sharma, K Wilson (1997) Metabolism of naphthalene, 1-naphthol, indene, and indole by Rhodococcus sp. strain NCIMB 12038. Appl Environ Microbiol 63 151-155. 

Investigation of a related indole template, however, yielded potent compounds, as exemplified by the sulphonamide derivative (33). Activity was improved further by introducing steric constraints to the sidechain and introduction of a 7-methyl substituent on the indole ring, leading to compound (34) [82]. Derivatives generally possessed only moderate pharmacokinetic properties however (clearance 25-45 ml/min/kg in dog), which was attributed to metabolic vulnerability of the indole (C2-C3) double bond. Attempts to block metabolism by C2, C3 di-methyl substitution resulted in the loss of oxytocin activity. 

Hardeland, R., Poeggeler, B., Behrmann, G. 8r Fuhrberg, B. (1996). Enzymatic and non-enzymatic metabolism of methoxyindoles. In ed. Hardeland, R. Metabolism and Cellular Dynamics of Indoles. (Goettingen University of Goettingen)... 

Figure 25. Early steps of anaerobic degradation of indole by Desulfobacterium indolicum and hypothetical metabolic steps of indole degradation by a denitrifying microbial community.

The anthranilate intermediate is believed to be metabolized to denitrogenated products. The list of proposed metabolites is also included in Fig. 25. A consortium of anaerobic and denitrifying bacteria was found to degrade indole via oxindole [341], but further details were not given to ensure if pathway 1 was followed. 

Some of the enzymes involved in the known pathways for the degradation of quinoline have been isolated and purified. However, not all enzymes have been identified, or characterized. In this section, we will consider the enzymes associated with the degradation of quinoline (and related compounds), carbazole and indole. To examine the enzymatic work, the reader is referred to the previous section, in which the metabolic pathways were detailed. 

In addition to the cultures identified for quinoline degradation, pyridine degraders were also found, namely Agrobacterium sp., Nocardia sp. strain PNO, Achromobacter sp., Rhodococcus opacus, and Arthrobacter crystallopoietes. The strain Alcaligenes sp. strain IN3 was reported to metabolize indole. 

Johansen, S. S. Licht, D., and Arvin, E., Metabolic Pathways of Quinoline, Indole and Their Methylated Analogs by Desulfobacterium Indolicum (DSM 3383). Appl Microbiol Biot, 1997. 47(3) pp. 292-300. 

Secoiridoids are complex phenols produced from the secondary metabolism of terpenes as precursors of several indole alkaloids (Soler-Rivas and others 2000). They are characterized by the presence of elenolic acid, in its glucosidic or aglyconic form, in their molecular structure. Oleuropein, the best-known secoiridoid, is a heterosidic ester of elenolic acid and 3,4- dihydroxyphenylethanol containing a molecule of glucose, the hydrolysis of which yields elenolic acid and hydroxytyrosol (Soler-Rivas and others 2000). 

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