Histamine-A-methyltransferase

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)...

Histamine is metabolized by histamine A-methyltransferase to A-methylhistamine, which is then deaminated by monoamine oxidase type B into methylimidazole acetic acid. Histamine is also fonnd in platelets, lenkocytes, and basophils in the skin, Inngs, and gastric mucosa, as well as to a certain extent in blood, plasma, sputum, gastric juice, blister fluid, and pns. Histamine is stored mosfly in mast cells. 

Histidine decarboxylase Diamine oxidase Histamine A -methyltransferase... 

Inhibits histamine-A -methyltransferase, increasing histamine levels... 

This is achieved by methylation and oxidation. In manunals, histamine is inactivated in two main ways— methylation of the imidazole ring effected by histamine A/-methyltransferase (HMT) and oxidative deamination of the primary amino group catalyzed by diamine oxidase (DAO)—to form A-methylhistamine and... 

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... 

Hepatitis 12 Histaminase 19, 20 Histamine human brain 60 kidney function, 74, 80 localization 4, 5 metabolism 17, 19 microcirculation 84 ff, 86 occurrence 49 ff pharmacology 70, 71 production 8 respiratory metabolism 89 turnover 23, 24 Histamine headache 126 Histamine-A-methyltransferase 17 Histidine decarboxylase 2, 7 Homoprotocatechuic acid see 3,4-Dihy-droxyphenylacetic acid Homovanillic acid see 3-Methoxy-4-hy-droxyphenylacetic acid 5-Hydroxindole acetic acid excretion 11, 12 microcirculation 86 occurrence 46 ff... 

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. 

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). 

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... 

Barnes, W. G., Grinde, E., Crawford, D. R., Herrick-Davis, K. and Hough, L. B. Characterization of a new mRNA species from the human histamine N-methyltransferase gene. Genomics S3 168-171,2004. 

Nishibori, M., Tahara, A, Sawada, K., Sakiyama, J., Nakaya, N. and Saeki, K. Neuronal and vascular localization of histamine N-methyltransferase in the bovine central nervous system. Eur. J. Neurosci. 12 415-424,2000. 

A high intracerebral level of S-adenosylhomocysteine may inhibit methylation reactions involving S-adenosyl-methionine. The metabolic repercussions would be extensive, including deficient methylation of proteins and of phos-phatidylethanolamine as well as an inhibition of catechol-O-methyltransferase and histamine-N-methyltransferase. 

Methyltransferases that utilize S-adenosyl-L-methionine as the methyl donor (and thus generating S-adenosyl-L-homocysteine) catalyze (a) A-methylation (e.g., norepinephrine methyltransferase, histamine methyltransferase, glycine methyltransferase, and DNA-(adenine-A ) methyltransferase), (b) O-methylation (e.g., acetylsero-tonin methyltransferase, catechol methyltransferase, and tRNA-(guanosine-0 ) methyltransferase), (c) S-methyl-ation (e.g., thiopurine methyltransferase and methionine S-methyltransferase), (d) C-methylation (eg., DNA-(cy-tosine-5) methyltransferase and indolepyruvate methyltransferase), and even (e) Co(II)-methylation during the course of the reaction catalyzed by methionine syn-thase. ... 

The inactivation of histamine is achieved both by enzymatic metabolism of the amine and by transport processes that reduce the concentration of the compound in the region of its receptors. Histamine metabolism occurs primarily through two pathways (Fig. 38.1). The most important of these involves histamine N-methyltransferase, which catalyzes the transfer of a... 

N-Methylation. Several enzymes are known that catalyze (V-methylation reactions. They include histamine (V-methyltransferase, a highly specific enzyme that occurs in... 

Histamine N-methyltransferase catalyzes the transfer of a methyl group from S-adenosyl-L-methionine to histamine to form N-methylhistamine. This assay is suitable for following activity during enzyme purification. 

Histamine was previously mentioned as a putative neurotransmitter (Chapter 12). It may have a role in sedation and wakefulness. In fact, drowsiness had been implicated previously with a possible inhibition of histamine-N-methyltransferase by antihistamines and subsequently with the blockade of central histaminergic receptors as well. However, it... 

Methylation is an important reaction in the biosynthesis of endogenous compounds such as adrenaline and melatonin, in the inactivation of biogenic amines such as the catecholamines, serotonine and histamine, and in modulating the activities of macromolecules, such as proteins and nucleic acids. The number of xenobiotics that are methylated is comparatively modest, yet this reaction is seldom devoid of pharmacodynamic consequences (toxication or detoxication). Reactions of methylation imply the transfer of a methyl group from the onium-type cofactor S-adeno-sylmethionine (SAM) to the substrate by means of a methyltransferase. The activated methyl group from SAM is transferred to the acceptor molecules R — XH or RX, as shown in Fig. 31.30. 

A/-Methylations are catalysed by several enzymes such as nicotinamide A -methyltransferase, histamine methyltransferase, phenylethanolamine iV-methyltransferase (noradrenaline Af-methyltransferase) and a non-specific amine N-methyltransferase (arylamine iV-methyltransferase, tryptamine iV-methyltransferase). S-Methylations are catalysed by the membrane-bound thiol methyltransferase and the cytosolic thiopurine methyltransferase. 

Acetylcholine is formed from choline (which is also an important constituent of phospholipids) and acetyl CoA under the catalytic influence of choline acetyl-ase. It is hydrolised by acetylcholinesterase or choline esterase. Two important steps in the formation of noradrenaline from tyr dopa decarboxylase and dopamine hydroxylase. Adrenaline is formed from noradrenaline by phenyl ethanolamine A -methyltransferase. Both noradrenaline and adrenaline are metabolised by catechol 0-methyl transferase or monoamine oxidase. Some later steps in their metabolism involve aldehyde dehydrogenase and alcohol dehydrogenase (aldehyde reductase), After hydroxylation to its 5-hydroxy derivative, tryptophan is converted by 5-hydroxytryptophan decarboxylase to 5-hydroxytryptamine (serotonin). The major routes of serotonin metabolism involve either monoamine oxidase or hydroxyindole 0-methyltransferase. Histamine is synthesised from histidine by histidine decarboxylase, and is metabolised by either diamine oxidase or histamine Af-methyltransferase. Gamma aminobutyric acid is formed by glutamate decarboxylase and metabolised by... 

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