Indoleacetic acid, from tryptophan

As soon as he had identified indoleacetic acid as a plant growth substance, Thimann proposed that it must be derived from tryptophan (III). Since tryptophan is the most prominent indole in plant tissues, occurring both in protein and as a free amino acid, this still seems reasonable. However, numerous workers have investigated various plant tissues for their capacity to produce indoleacetic acid from tryptophan and in aU cases the capacity of their systems has been feeble indeed. The best conversions obtained have fallen in the range of 0.3%, and most are less. As it is not difficult to obtain comparable amounts of indoleacetic acid from tryptophan non-enzymatically under mild conditions, the specificity of the systems investigated is still... 

Important indole derivatives (see Scheme 2) include (i) indigo, a vat dye known and widely used since antiquity, and originally obtained from indican, a (3-glucoside of indoxyl which occurs in some plants. Indigo is now prepared synthetically. Tyrian purple, a natural dye used since classical times, is 6,6 -dibromoindigo (ii) the numerous indole alkaloids, with complex derivatives such as yohimbine and strychnine (iii) tryptophan, an essential amino acid found in most proteins. Its metabolites include skatole and tryptamine and (iv) 3-indoleacetic acid, which is important as a plant growth hormone. 

Metabolic studies by Milne et al. (M8) showed that in Hartnup disease the renal aminoaciduria is more constant than the excessive excretion of indican and indolic acids (indoleacetic acid, indolelactic acid, and indoleacetylglutamine). After ingestion of L-tryptophan in this disease there is usually delayed and incomplete absorption from the gut of the amino acid which is partly converted, by intestinal bacteria, to indole... 

Besides being fundamental constituents of proteins they are the parent substances from which powerful hormones are derived, for example, adrenaline (epinephrine), noradrenaline (norepinephrine), thyroxine and related substances, 5-hydroxytryptamine (enteramine, serotonin), and the plant hormone indoleacetic acid. Tryptophan is also the precursor of the B vitamin nicotinic acid and hence of part of the important pyridine nucleotides. All three aromatic amino acids are potential precursors of other substances having powerful physiological activity, for example, many of the alkaloids. Errors in the metabolism of the aromatic amino acids in man can give rise to sometimes serious, but fortunately comparatively rare, disorders such as alkaptonuria and phenylketonuria. The numerous metabolic pathways involved in aromatic amino acid metabolism therefore make an important as well as an interesting study. 

Tryptophan can be converted to indolepyruvic acid either by oxidative deamination or by transamination (e.g., 739, 912) and the indolepyruvic acid can give rise to indoleacetic acid. The fate of indoleacetic acid formed by the bacterial flora of the mammalian gut is discussed below. Bacterial indolelactic acid (e.g., 757) is presumably derived from indolepyruvic acid, but indolelactic acid excreted by mammals (e.g. 17) may be of true mammalian rather than bacterial origin. Indolepropionic acid can also be formed by bacteria (e.g., 412, 633), but further metabolism in mammals of any indolepropionic acid formed in the gut is still obscure (904). Skatole (3-methylindole) has long been known as a product of bacterial decomposition of protein and is formed from tryptophan not only by the bacterial flora of the gut but also in putrefying secretions, e.g., sputum (756). It may well arise by decarboxylation of indoleacetic acid. 

Tryptophan has been clearly established as the precursor of indoleacetic acids in both plants (e.g., 303, 921, 922) and fungi (e.g., 864), and in plant tumor tissue (e.g., 378, 948). Two routes are possible for indoleacetic acid formation from tryptophan as follows ... 

There is evidence that both these routes can occur. The enzymes converting tryptophan to indoleacetic acid can be obtained in maize embryo juice the tryptophan is thought to arise from the endosperm (964). Indolepyruvic acid is also present in maize endosperm (837, 838), suggesting it to be an intermediate. On the other hand, tryptamine is converted to indoleacetic acid in plants (304, 815) and the amine oxidase responsible has been studied by Kenten and Mann (464). Consideration of the biogenesis of alkaloids, discussed later, suggests that both tryptamine and indoleacetaldehyde are likely to occur in plants. 

Tryptamine (XIV) is found in some species of Acacia (7). It may be formed by putrefaction bacteria from tryptophan-containing media (63). N-Methyltryptamine (XV) is said to be idential with dipterin which occurs in Girgensohnia diptera Bge. and Arthrophytum leptocladum Popov (64). Results of pharmacological studies show that tryptamines are musculo-tropic and not sympathomimetic (65). They do not dilate the rabbit s pupil and they contract both the rabbit s isolated intestine and guinea pig s uterus. The pressor action of tryptamine is higher than that of N-methyltryptamine. The former is metaboMzed to indoleacetic acid by deamination in the body (13). 

Two pathways have been envisaged for the biosynthesis of 2-aminoacetophenone from tryptophan, to explain how it is formed in wine. The first pathway is physicochemical, via indoleacetic acid, while the second is enzymatic, involving cynurease (Rapp et al., 1998 Gebner et al., 1998) (Figure 8.32). 

Serotonin is formed directly from tryptophan via hydroxylation and decarboxylation, and is metabolized to 5-hydroxy-3-indoleacetic acid by monoamine oxidase (MAO) and excreted. 

Serotonin S-hydroxytryptamine, M, 176.2, a plant and animal hormone. It is produced by hydroxylation of L-tryptophan to 5-hydroxytryptophan, followed by decarboxylation. The synthesis occurs in the central nervous system, lung, spleen and argentaffine light cells of the intestinal mucosa. S. is stored in thrombocytes and mast cells of the blood. It acts as a Neuro-transmitter (see), stimulates peristalsis of the intestine, and causes a dose-dependent constriction of smooth muscle. It stimulates the release from arterial endothelium of a dilator substance which counteracts its primary constricting effect [T.M. Cocks X A. Angus Nature 305 (1983) 627-630]. S. is a precursor of the hormone Melatonin (see). It is inactivated and degraded by monoamine oxidases and aldehyde oxidases to 5-hydroxy-indoleacetic acid. 

Amino-iV-methyl tryptamine (XV), as well as amino-V,V-dimethyl tryptamine (XXI) and its A -oxide (XVI), all occurring in plants, have been shown to be oxidized to indoleacetic acid by mouse liver homogenates, but these reactions have not yet been observed with plant enzymes. It is noteworthy that these compounds might be derived from the naturally occurring amino-methylated derivatives of tryptophan, namely abrine (VII) and hyp-aphorine (XII). 

Oxidation of the side chain of tryptophan results in the formation of indole-3-acetic acid, the auxin of plant physiology and also a metabolite of animals. Enzymes from several plant sources have been reported to oxidize indoleacetic acid, but in no case has the product been identified. Without more precise knowledge about the properties of the reactions obtained with various preparations, it is not possible to conclude that the same type of enzyme or reaction is being studied with crude enzymes from peas (Tang and Bonner, 1947) or molds (Ray and Thimann, 1956), for example, or with purified peroxidases (Kenten, 1955). 

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