Indoleacetic acid, oxidation

MATO M.C., GONZ EZ-ALONSO L.M. and MENDEZ J. 1972. Inhibition of enzymatic indoleacetic acid oxidation by fulvic acids. Soil Biology and Biochemistry, 4, 475-478. 

If the enzymes that oxidize indoleacetic acid are found in general to utilize nonspecific electron acceptors in the presence of hydrogen peroxide, it must be concluded that the mechanism of indoleacetic acid oxidation is primarily a peroxidation, not an oxygenation. At the present time, however, the possibility must also be considered that the role of hydrogen peroxide and substrate is to establish the ferrous state of the enzyme required for oxygenase activity, as in the case of tryptophan pyrrolase. 

Indium-tin-oxide anode, 22 215, 216 Indium trichloride, 14 197, 201 Indo-3-lyl acetic acid, 13 284 Indole-3-acetic acid, 13 35, 38. See also Indoleacetic acids (IAAs) Indole-3-butyric acid, 13 25t... 

C. C. C. Vidigal, A. Faljoni-Alario, N. Duran, K. Zinner, Y. Shimizu, and G. Cilento, Electronically excited species in the peroxidase catalyzed oxidation of indoleacetic acid. Effect upon DNA and RNA, Photochem. Photobiol. 30, 195-198 (1979). 

The principal reason that DMT must be administer parenterally is its rapid and efficient metabolism. It can be oxidized to the N-oxide. It can be cyclized to b-carbolines, both with and without an N-methyl group. It can be N-dealkylated to form NMT and simple tryptamine itself. Best known is its oxidative destruction, by the monoamine oxidase system, to the inactive indoleacetic acid. There is a wild biochemical conversion process known for tryptophan that involves an enzymatic conversion to kynurenine by the removal of the indole-2-carbon. A similar product, N,N-dimethylkynuramine or DMK, has been seen with DMT, when it was added to whole human blood in vitro. 

Oxidation of DNA, pyrimidines, and purines Inhibition of polysaccharide synthesis Oxidation of indoleacetic acid Inhibition of cellulose synthetase, phospho-glucomutase, UDPG pyrophosphorylase... 

On account of the activity of these plant extracts and the isolation from them of iV,iV-dimethyltryptamine, the physiological activity of this base in humans is of interest. When injected intramuscularly, it causes hallucinations and illusions, which are characterized by their rapid appearance and brief duration (80). Apparently, dimethyltrypt-amine is rapidly metabolized and excreted mainly as indoleacetic acid, although the urine is enriched with 5-hydroxyindoleacetic acid whether this is the result of oxidation at the 5-position or stimulation of the metabolism of serotonin in the brain is not yet known (80). 

As pointed out previously, most herbicides have been discovered using random screening programs rather than from an applied rational approach to herbicide design, target, and synthesis. A few attempts to rationally design herbicides chose Inhibition of sites of photophosphorylation uncouplers (284). glycol ate oxidase (285). oxidation of Indoleacetic acid (lAA) by peroxidase (286). and secondary plant metabolism, I.e., phenlyalanine ammonia-lyase (2SZ)... 

LXXXIV) or undergo further oxidation and base-catalyzed decarboxylation (LXXXVI) to the labile nonisolable 3-methyleneoxindole (LXXXVIIa), characterizable as the sodium bisulfate addition product (LXXXVIIb). 8-Methylene oxindole (LXXXVIIa) bears a spectral resemblance to the oxidation product of auxin produced by peroxidase or indoleacetic acid oxidase from the fungus Omphalia ftavida (Ray and Thimann, 1956). 

Yamazaki, Mason and Piette [63-65] have investigated the mechanism of action of peroxidases using flow ESR apparatus. The peroxidase used (from Japanese turnips) catalyses the oxidation of a number of substrates such as indoleacetic acid, dihydroxyfumarate and triose reductone by hydrogen peroxide. They were able to demonstrate directly the presence of free radical intermediates, a number of which could be identified from their hyperfine structure, and to show a correlation between ESR signal intensity and the kinetics expected for the reaction. This was strong evidence for a mechanism concerning one-electron transfer steps. The steady state concentration of free radicals was proportional to the square root of the enzyme concentration and the main decay route of the radicals was via dismutation. 

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 appears to be converted to a larger number of metabolites than any of the other amino acids. The degradation of tryptophan in animals occurs mainly in two pathways, I and II (Figure 4.1). The first major pathway (I), initiated by the action of tryptophan dioxygenase, involves oxidation of tryptophan to N - fc > r my I ky n urenine and the formation of a series of intermediates and byproducts, most of which appear in varying amounts in the urine, the sum of which accounts for the total metabolism of tryptophan, approximately. The second pathway (II) involves hydroxylation of tryptophan to 5-hydroxytryptophan and decarboxylation of this compound to 5-hydroxytryptamine (serotonin), a potent vasoconstrictor found particularly in the brain, intestinal tissues, blood platelets, and mast cells. A small percentage (3%) of dietary tryptophan is metabolized via the pathway (III) to indoleacetic acid. Other minor pathways also exist in animal tissues. 

Indoleacetic acid (lAA) (17) is involved in many aspects of plant growth and development (Bonner and Varner, 1976 Kosuge and Sanger, 1986). This hormonal substance is derived in most plants by conversion of tryptophan to indole 3-pyruvic acid (15) (tryptophan amino transferase), decarboxylation to the indole 3-acetaldehyde (16) (indole pyruvate decarboxylase), and oxidation to indole 3-acetic acid (17) (indole acetaldehyde oxidase) (Fig. 7.6) (Goodwin and Mercer, 1983). 

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). 

It is similarly well established that the removal of indoleacetic acid from metabolic availability may also follow more than one pathway. These include both oxidation by light and by enzymes, and con j ugation to other compounds. 

Other studies of the fate of indoleacetic acid in plant tissues have concentrated on non-oxidized products. It has been shown that indoleacetic acid can readily be esterified to its ethyl ester (XXIII) by plant enzymes, and there is some evidence this that is a naturally occurring substance. Similarly, when indoleacetic acid is applied to plant tissue it is rapidly conjugated into indoleacetamide (XVIII) and indoleacetylaspartic acid (XXII). The details of this process have been extensively studied by Andreae and his coworkersi, but the nature of the enzymes involved remains unclarified. AU three of these compounds can produce auxin effects when applied to tissue, hence they can act as indoleacetic acid precursors. However, the kinetics of the reactions which form them appear to favor the conjugated substances and they are more correctly considered as products rather than precursors of... 

Tryptamine is oxidatively deaminated to indoleacetic acid. A, -dimethyl-tryptamine, " " found by us in human blood and urine, is probably produced by methylation of the mono-methyl derivate, which so far has not been traced in man. 

Auxin Formation. Oxidation or transamination leads to the formation of indolepyruvic acid. Decarboxylation of the keto acid is presumed to result in the formation of indoleacetaldehyde, which can be oxidized by an aldehyde oxidase to indoleacetic acid (V). This compound is excreted by humans, but appears to be the natural auxin, a plant growth hormone. Degradation of auxin by plants appears to involve a peroxidase acting as an oxidase. Horseradish peroxidase plus Mn++ carry out the same... 

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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