Imidazoleacetate

Metabolism. MetaboHsm of histamine occurs via two principal enzymatic pathways (Fig. 1). Most (50 to 70%) histamine is metabolized to /V-methylhistamine by A/-methyltransferase, and some is metabolized further by monoamine oxidase to /V-methy1imidazo1eacetic acid and excreted in the urine. The remaining 30 to 40% of histamine is metabolized to imidazoleacetic acid by diamine oxidase, also called histaminase. Only 2 to 3% of histamine is excreted unchanged in the urine. 

Granerus, G. (1968). Effects of oral histamine, histidine, and diet on urinary excretion of histamine, methylhistamine, and l-methyl-4-imidazoleacetic acid in man, Scand. J. Clin. Lab. Invest., 10, suppl., 49. 

IMIDAZOLEACETATE HYDROXYLASE ISOVALERYL-CoA DEHYDROGENASE KYNURENINE 3-HYDROXYLASE d-LACTATE DEHYDROGENASE (CYTOCHROME)... 

IMIDAZOLEACETATE HYDROXYLASE NADH-CYTOCHROME bs REDUCTASE NADH DEHYDROGENASE... 

IMIDAZOLEACETATE HYDROXYLASE INDOLEAMINE 2,3-DIOXYGENASE myo-INOSITOL OXYGENASE JUGLONE MONOOXYGENASE KYNURENINE 3-HYDROXYLASE LACCASE... 

An alternative pathway of histamine metabolism involves oxidative deamination by the enzyme diamine oxidase (histaminase) to form 5-imidazoleacetic acid. Diamine oxidase is present in both tissues and blood and plays a particular role in metabolizing the large concentrations of histamine that may be present in food. An additional metabolite, A-acetyl histamine (a conjugate of acetic acid and histamine), can be produced if histamine is ingested orally. This product may result from metabolism of histamine by gastrointestinal tract bacteria. Because of its rapid breakdown after oral administration, histamine produces few systemic effects when given by this route. 

Imidazoleacetic acid riboside Figure 4.11 Histamine metabolism. 

Histamine is formed by decarboxylation of the amino acid l -histidine, a reaction catalyzed in mammalian tissues by the enzyme histidine decarboxylase. Once formed, histamine is either stored or rapidly inactivated. Very little histamine is excreted unchanged. The major metabolic pathways involve conversion to /V-methylhistamine, methylimidazoleacetic acid, and imidazoleacetic acid (IAA). Certain neoplasms (systemic mastocytosis, urticaria pigmentosa, gastric carcinoid, and occasionally myelogenous leukemia) are associated with increased numbers of mast cells or basophils and with increased excretion of histamine and its metabolites. 

A minor route for histamine catabolism involves histamine conversion to imidazoleacetic acid [via diamine oxidase (histaminase)]. In the major route histamine is converted to methylhistamine [via histamine jV-methyl transferase] which is then converted to methylimi-dazoleacetic acid [via MAO]. A large number of MAO inhibitors have been isolated from plants (Table 6.5). 

Raman spectroscopy showed the presence of Co2C and Co3C units in Co/C60 nano-composite materials.327 The IR and Raman spectra of Co(II), Ni(II) and Cu(II) complexes of 4-imidazoleacetic acid (HIA) have been reported, M(IA)2(L)2, where L = HzO, MeOH. There is evidence for extensive mixing of Cu-N and Cu-O modes.328... 

A / iV-imidazoleacetic acid (I A A, 99), a metabolite of histidine 100, and histamine S found in brain and cerebrospinal fluid , has been synthesized by oxidizing A, Af-DL-histidine with sodium hypochlorite, subsequent acid hydrolysis of the formed A, A -imidazoleacetonitrile 101 and separation of the product 99 on an anion exchange column with 0.1 N acetic acid (equation 42). The A, A -IAA obtained served as an internal standard for GC-MS analysis of physiological fluids. 

Histamine is formed from the amino acid histidine and is stored in high concentrations in vesicles in mast cells. Histamine is metabolized by the enzymes monoamine oxidase and diamine oxidase. Excess production of histamine in the body (by. for example, systemic mastocytosis) can be detected by measurement of imidazoleacetic acid (its major metabolite) in tbe urine. Because it is released from mast cells in response to IgE-mediated (immediate) allergic reactions, this autacoid plays an important pathophysiologic role in seasonal rhinitis (hay fever), urticaria, and angioneurotic e ma. Histamine also plays an important physiologic role in the control of acid secretion in the stomach and as a neurotransmitter. 

Imidazoleacetate and i.-lysine monooxygenases from pseudomonads were obtained in crystalline form. Both enzymes were established to contain FAD probably as a sole cofactor. Available evidence indicates that the reaction catalyzed by these enzymes involves the reduction of FAD, the monooxygenation of substrate, and the reoxidation of reduced FAD. The mechanism of activating molecular oxygen by these FAD-containing monooxygenases is discussed. 

To clarify the reaction mechanism of monooxygenase, we have recently purified two monooxygenases from pseudomonads. Imidazoleacetate monooxygenase (5) and L-lysine monooxygenase (JO) were obtained in crystalline form, and both were shown to be flavoproteins. The former requires an exogenous hydrogen donor, but the latter utilizes the hydrogen atoms of L-lysine. 

Imidazoleacetate monooxygenase was purified about 250-fold from a cell-free extract of a pseudomonad and was obtained in crystalline form (Figure 1). The specific activity of the crystalline enzyme was 25.0 /xmoles/min./mg. protein, and on the basis of a molecular weight of 90,000 its molecular activity was estimated to be 2000 at 24°C. 

The enzyme catalyzes the incorporation of one atom of oxygen into imidazoleacetate, and the accumulation of imidazoloneacetate was observed. The reaction product was unstable and decomposed spontaneously. NADH (nicotinamide adenine dinucletotide hydrate) was consumed as a hydrogen donor. The enzyme assay was carried out either by the spectrophotometric measurement of NADH oxidation or... 

Table I. Estimations of Iron and Copper of Imidazoleacetate and L-Lysine Monooxygenases, /miole...

Reduction of the enzyme-bound FAD was observed on adding sodium dithionite at pH 10.5 (Figure 3). FAD reduction was also observed on adding NADH both in the presence of imidazoleacetate and in its absence (Figure 3). An absorption spectrum characteristic of the semiquinoid form of FAD appeared when the enzyme was half reduced with sodium dithionite but not with NADH. 

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