Histamine oxidase

The continuous measurement of histamine released from rat basophilic leukaemia cells has been recently reported by Niwa [190], who coupled a microdialysis probe with a histamine oxidase-based carbon electrode obtained by coating the enzyme on the top of an Os-gel-HPR layer. For the exclusion of electrochemically active compounds, they suggested an overcoating of Nafion. In addition, a sensor using micro-machining techniques has been fabricated by the authors and apphed to the monitoring of histamine release from a small mast cell colony. 

Histamlnase lyiamitte oxidase benzylamine oxj. dase histamine deaminase histamine oxidase E.C- 1.4,3,6. A copper contg enzyme present in tissues esp in kidneys and in the intestinal mucosa. Attacks diamines such as histamine in tbe body by oxidaiive deamination Best. J. Physiol 67, 256 (1929) Zeller Heiv. Chim. Acta 2l, 880 (1938) Advan. Entymol 2, 93 (1942). Extraction from hog kidneys Swedin. Acta Med. Scand. 114, 21 (1943). Identity with diamine oxidase Zeller Fed. Proc. 24, 764 (1965). Appears to have the general properties of a flavoprotein. Review E. A, Zeller "Diamine Oxidases in The Enzymes, vol. 8, P. D. Boyer et al, Eds. (Academic Press, New York 2nd ed., 1963) pp 313-335 Buffoni Pharmacol. Rev. ]8, 1163-1199 (1966) Hansson Scand- J. Clin. Lab, Invest, vol 31, suppl. 129 7 0973). 

In the amine oxidase from Escherichia coli, the topa quinone was confirmed by a detailed analysis of the cofactor dipeptide X-Asp [67] and the resonance Raman spectrometry of the enzyme and its derivatives[68,69]. The primary structure of the enzyme also contains the cofactor consensus sequence [70]. More bacterial genes were shown to encode proteins containing the topa quinone consensus sequence, such as amine oxidase from Klebsiella aerogenes [71], phenethylamine oxidase and histamine oxidase from Arthrobacter globiformis [72,73], and methylamine oxidase from Arthrobacter strain PI [74]. Amino acid sequences around the position of the cofactor for selected amine oxidases from various sources are given in Table 1. 

Recent spectroscopic studies suggest, however, that this could happen only with the assistance of an active site lysyl residue [148]. Such a lysyl residue is found in the crystal structure of the active site of pea seedling amine oxidase [29], but is absent from E. coli amine oxidase [28]. The process of redox-active cofactor formation in phenethylamine oxidase and histamine oxidase of A. globiformis was recently analyzed by Raman spectroscopy using isotopic exchange. It was found that the oxygen on the... 

S. Iwaki, M. Ogasawara, R. Kurita, O. Niwa, K. Tanizawa, Y. Ohashi, K. Maeyama, Real time monitoring of histamine released from rat basophilic leukemia (RBL-2H3) cells with a histamine microsensor using recombinant histamine oxidase, Analytical Biochemistry 2002, 304, 236. 

Ito, T., Hiroi, T., Amaya, T., Kaneko, S., Araki, M., Ohsawa, R., Yamamaura, A., and Matsumoto, K. (2009) Preliminary study of a microbeads based histamine detection for food analysis using thermostable recombinant histamine oxidase from Arthrobacter crystallopoietes KAIT-B-007. Talanta, 77, 1185-1190. 

Amine oxidase is widely distributed among vertebrate and invertebrate tissues, and attacks many aliphatic and aromatic amines, including adrenaline and tyramine. It is distinct from histamine oxidase, which oxidises diamines. 

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. 

Histamine AND histamine antagonists). It is formed from histidine by the enzyme L-histidine decarboxylase. In the periphery, histamine is stored ia mast cells, basophils, cells of the gastric mucosa, and epidermal cells. In the CNS, histamine is released from nerve cells and acts as a neurotransmitter. The actions of histamine ate terrninated by methylation and subsequent oxidation via the enzymes histamine-/V-methyltransferase and monoamine oxidase. 

L-Tyrosine metabohsm and catecholamine biosynthesis occur largely in the brain, central nervous tissue, and endocrine system, which have large pools of L-ascorbic acid (128). Catecholamine, a neurotransmitter, is the precursor in the formation of dopamine, which is converted to noradrenaline and adrenaline. The precise role of ascorbic acid has not been completely understood. Ascorbic acid has important biochemical functions with various hydroxylase enzymes in steroid, dmg, andhpid metabohsm. The cytochrome P-450 oxidase catalyzes the conversion of cholesterol to bUe acids and the detoxification process of aromatic dmgs and other xenobiotics, eg, carcinogens, poUutants, and pesticides, in the body (129). The effects of L-ascorbic acid on histamine metabohsm related to scurvy and anaphylactic shock have been investigated (130). Another ceUular reaction involving ascorbic acid is the conversion of folate to tetrahydrofolate. Ascorbic acid has many biochemical functions which affect the immune system of the body (131). 

Histamine is synthesized from the amino acid histidine via the action of the specific enzyme histidine decarboxylase and can be metabolized by histamine-TV-methyl transferase or diamine oxidase. Interesting, in its role as a neurotransmitter the actions of histamine are terminated by metabolism rather than re-uptake into the pre-synaptic nerve terminals. 

Figure 13.4 Histamine synthesis, metabolism and receptors. Current knowledge does not justify presentation of a schematic histaminergic synapse. (1) Histidine decarboxylase (2) histamine-A-methyltransferase (3) mono amine oxidase (MAOb)...

Monoamine oxidase inhibition Serotonin reuptake inhibition Norepinephrine reuptake inhibition Dopamine reuptake inhibition a2-Adrenergic receptor blockade Serotonin-2A receptor blockade Serotonin-2C receptor blockade Serotonin-3 receptor blockade op-Adrenergic receptor blockade Histamine-1 receptor blockade Muscarinic cholinergic receptor blockade... 

HA turnover is rapid in the brain, with a half-life of about 30 min. This can change very quickly depending on neuronal activity. There is no high-affinity uptake system for HA once released, HA is inactivated by catabolism. In the brain, released HA is methylated almost exclusively by the enzyme histamine-N-methyltransferase (E.C. 2.1.1.8). The tele-methyl-HA is subsequently degraded by monoamine oxidase-B (MAO-B) and aldehyde dehydrogenase to produce tele-methylimidazoleacetic acid (Brown et ah, 2001). 

L The answer is d. (Hardman, p 906.) Cimetidine slows the metabolism of Ca channel blockers, which are substrates for hepatic mixed-function oxidases. Inhibition of cytochrome P450 activity is peculiar to cimetidine and is not a mechanism of action of other histamine 2 (Hz) blockers. 

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... 

FIGURE 14-3 Synthesis and metabolism of histamine. Solid lines indicate the pathways for histamine formation and catabolism in brain. Dashed lines show additional pathways that can occur outside the nervous system. HDC, histidine decarboxylase HMT, histamine methyltransferase DAO, diamine oxidase MAO, monoamine oxidase. Aldehyde intermediates, shown in brackets, have been hypothesized but not isolated. 

Beyond their action upon SERT and NET, venlafaxine (1), milnacipran (2) and duloxetine (3) are remarkably selective molecules. All three of them have displayed very low in vitro affinity Ki > 3(X)0 nM) for ai- and a2-adrenergic, histamine Hj, muscarinic, and DA D2 receptors, consistent with favorable side-effect profiles. Venlafaxine (1) and duloxetine (3) also have low affinity for a number of serotonergic receptors, and do not inhibit monoamine oxidase A or B. An expanded in vitro receptor profile of >50 receptors and binding sites... 

With the introduction of the SSRIs, the safety and tolerability of antidepressants improved remarkably. As a class, these medications have little or no affinity for cholinergic, (3-adrenergic or histamine receptors and do not interfere with cardiac conduction. They are well tolerated by patients with heart disease and by the elderly, who are especially sensitive to the anticholinergic and orthostatic effects of the tricyclic antidepressant agents (TCAs) and monoamine oxidase inhibitors (MAOIs). 

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. 

Buspirone does not affect either monoamine oxidase A (MAO-A) or MAO-B (Jann, 1988 Cole and Yonkers, 1995). There is also no evidence of action on the adenosine, cholinergic (mucarinic), glutamate, glycine, histamine, or opiate systems (Jann, 1988). 

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