Imidazole-4-acetic acid

Because esters 745 a, b of imidazole-acetic acid are unstable when stored for long periods, owing to intramolecular catalysis by the imidazole moiety, the esters should be converted into their salts or free acids and stored as such. Only tert-butyl imidazole-(4,5)acetates derived from tert-butyl 4-chloroacetoacetate seem to be stable [232, 233]. N-alkyl-substituted amidines give rise to a mixture of alkyl N-alkylimidazole-4- and 5-acetates [232, 233]. 

Hosli, L. Haas, H. L. (1971). Effects of histamine, histidine and imidazole acetic acid on neurones of the medulla oblongata of the cat. Experientia 27, 1311-12. 

Biosynthesis is performed in one step by the enzyme L-histidine decarboxylase (HDC, E.C. 4.1.1.22). Histamine metabolism occurs mainly by two pathways. Oxidation is carried out by diamine oxidase (DAO, E.C. 1.4.3.6), leading to imidazole acetic acid (IAA), whereas methyla-tion is effected by histamine N-methyltransferase (HMT, E.C. 2.1.1.8), producing fe/e-methylhistamine (t-MH). IAA can exist as a riboside or ribotide conjugate. t-MH is further metabolized by monoamine oxidase (MAO)-B, producing fe/e-methylimidazole acetic acid (t-MIAA). Note that histamine is a substrate for DAO but not for MAO. Aldehyde intermediates, formed by the oxidation of both histamine and t-MH, are thought to be quickly oxidized to acids under normal circumstances. In the vertebrate CNS, histamine is almost exclusively methylated... 

ICAM intercellular adhesion molecule t-MIAA tele methyl imidazole acetic acid... 

Histamine is rapidly degraded by oxidative de-samination by the diaminooxidase histaminase, acetylation of the NH2-group, methylation of the ring and oxidation of the methylhistamines by the mono-aminoxidase. The main metabolites are the N-methyl-imidazole acetic acid and the imidazole acetic acid. Histamine interacts with at least four different specific receptors Hi to H4 (see Table 1). 

Other products from histidine include the hormonal substance histamine formed by decarboxylation, the oxidation product, imidazole acetic acid, and N5- and A/c-methylhistidines. Histamine plays a role in release of gastric secretions and allergic responses (Chapter 5). Drugs (antihistamines) that inhibit its release are in widespread use. The unusual amino acid diphthamide has an unknown function in pro-... 

Interactions with Histidine. Imidazole lactic acid and imidazole acetic acid were identified as breakdown products when histidine was reacted with methyl linoleate, methyl linoleate hydroperoxide or hexanal for 3 weeks at 25°C and 51°C (33). It was postulated that these compounds were formed via free radical reactions. Two other products were also produced which yielded histidine upon acid hydrolysis. These were thought to be Schiff s base compounds arising... 

Once released, histamine is rapidly metabolized in vivo (based on products from radiolabeled histamine administered intradermally) to nearly inactive metabolites by two major pathways N-methylation, and oxidation (Fig. 37.3). Methylation (S-adenosylmethionine), which is catalyzed by the intracellular enzyme N-methyltransferase, yields an inactive metabolite. A portion of the N-methylated metabolite is oxidized sequentially via monoamine oxidase and then via aldehyde oxidase to the corresponding N-methylimidazole acetic acid. Histamine also is oxidized to imidazole acetic acid by diamine oxidase (histaminase). A small amount of this acid intermediate is converted to the corresponding ribotide, an unusual metabolite (5). 

Histidine with peroxidizing lipid was altered both at the a-carbon and the imidazole side chain (23, 35). Histamine, imidazole acetic acid and imidazole lactic acid evidently... 

Methylated imidazole derivatives, imidazole acetic acid riboside (D 20) Urine... 

Imidazolone propionate hydrolase catalyzes the enzymatic cleavage of the imidazole ring to yield formi-minoglutamate. The rat liver enzyme has been partially purified. In addition to the enzymic conversion, two nonenzymic spontaneous reactions yield N-formyl-isoglutamine and 4-oxoglutamic acid. In addition to the oxidative pathways for histidine, there exist three other pathways for its use protein synthesis, decarboxylation to yield histamine (see Inflammation), and transaminase. The activity of histidine pyruvic transamination in rat liver is three times that of histidase. The product of the transaminase reaction is imidazole pyruvic acid, which in turn is converted to imidazole acetic acid. 

Gas Chromatographic Analysis of Histamine Metabolism in Urine. Quantitative Determination of Ring-Methylated Imidazole-Acetic Acids in Healthy Man... 

The oxidative deamination of histamine, in the course of which imidazol-acetic acid is formed, is catalysed by diamine-oxidase and also by monoamine-oxidase. By means of a specific histamine-A -methyltransferase, histamine is transformed into 1,4-methylhistamine, which is further... 

Imidazole acetic acid > thyrotoxicosis hyperthyroidism hypothyroidism chronic atrophic dermatitis mastitis carcinoma of the mamma carcinoma of the lung myotonic dystrophy normal ... 

Fig. 5. Br0nsted plot for a series of imidazole compounds, and the histidine residue of lysozyme, a-lytic protease, and S.G. trypsin. The data for hydroxymethylimidazole (1), imidazole (2), a-N-acetylhistidine (3), L-jJ-imidazole lactic acid (4), and imidazole acetic acid (5) are taken from Reference 6, and the line is a linear regression on these data. The parameters for a-lytic protease ( ), S.G. trypsin ( ), and lysozyme (O) are those used to draw the solid lines of Figures 2, 3, and 4, respectively.

Imamura, I., Watanabe, T., Maeyama, K., Kubota, A., Okada, A., and Wada, H., 1984, Effect of food intake on urinary excretions of histamine, N -methylhistamine, imidazole acetic acid and its conju-gate(s) in humans and mice, J. Biochem. 96 1931-1937. 

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