Histamine metabolism histidine

Histamine synthesis in the brain is controlled by the availability of L-histidine and the activity of histidine decarboxylase 254 Histamine is stored within and released from neurons but a neuronal transporter for histamine has not been found 254 In the vertebrate brain, histamine metabolism occurs predominately by methylation 254... 

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... 

Histamine metabolism differs from that of classical neurotransmitters because histamine is so widely distributed in the body. The highest concentrations in human tissues are found in the lung, stomach, and skin (upto 33 ug/g tissue). Histamine metabolic pathways are simple histamine is produced from histidine in just one step (see figure 4.11). The principal production takes place in the mast cells of the peritoneal cavity and connective tissues. The gastric mucosa is another major storage tissue. Histamine can be found in the brain as well. 

Amino acid decarboxylations are involved in the synthesis of several metabolically important amines, e.g., 5-hydroxytryptamine (serotonin) from tryptophan, histamine from histidine, and y-aminohutyric acid (GABA) from glutamate. 

Certain amino acids and their derivatives, although not found in proteins, nonetheless are biochemically important. A few of the more notable examples are shown in Figure 4.5. y-Aminobutyric acid, or GABA, is produced by the decarboxylation of glutamic acid and is a potent neurotransmitter. Histamine, which is synthesized by decarboxylation of histidine, and serotonin, which is derived from tryptophan, similarly function as neurotransmitters and regulators. /3-Alanine is found in nature in the peptides carnosine and anserine and is a component of pantothenic acid (a vitamin), which is a part of coenzyme A. Epinephrine (also known as adrenaline), derived from tyrosine, is an important hormone. Penicillamine is a constituent of the penicillin antibiotics. Ornithine, betaine, homocysteine, and homoserine are important metabolic intermediates. Citrulline is the immediate precursor of arginine. 

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. 

Histamine synthesis from 1-histidine can be selectively inhibited by a-fluoromethylhistidine. Metabolism by... 

Histamine is a critical mediator in anaphylactic reactions. It is a diamine produced by decarboxylation of the amino acid histidine in the Golgi apparatus of mast cells and basophils. Once secreted, it is rapidly metabolized by histamine methyltransferase [2]. Plasma histamine levels are elevated in anaphylaxis, reaching a concentration peak at 5 min and declining to baseline by 30-60 min [3]. Therefore, histamine samples for assessing an anaphylactic reaction should be obtained within 15 min of the onset of the reaction. Urinary metabolites of histamine may be found for up to 24 h. 

Histamine is synthesised by decarboxylation of histidine, its amino-acid precursor, by the specific enzyme histidine decarboxylase, which like glutaminic acid decarboxylase requires pyridoxal phosphate as co-factor. Histidine is a poor substrate for the L-amino-acid decarboxylase responsible for DA and NA synthesis. The synthesis of histamine in the brain can be increased by the administration of histidine, so its decarboxylase is presumably not saturated normally, but it can be inhibited by a fluoromethylhistidine. No high-affinity neuronal uptake has been demonstrated for histamine although after initial metabolism by histamine A-methyl transferase to 3-methylhistamine, it is deaminated by intraneuronal MAOb to 3-methylimidazole acetic acid (Fig. 13.4). A Ca +-dependent KCl-induced release of histamine has been demonstrated by microdialysis in the rat hypothalamus (Russell et al. 1990) but its overflow in some areas, such as the striatum, is neither increased by KCl nor reduced by tetradotoxin and probably comes from mast cells. 

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)...

Figure 6.1 Histamine synthesis and metabolism in neurons. L-histidine is transported into neurons by the L-amino acid transporter. Once inside the neuron, L-histidine is converted into histamine by the specific enzyme histidine decarboxylase. Subsequently, histamine is taken up into vesicles by the vesicular monoamine transporter and stored there until released. In the absence of a high-affinity uptake mechanism in the brain, released histamine is rapidly degraded by histamine methyltransferase, which is located postsynaptically and in glia, to telemethylhistamine, a metabolite that does not show any histamine-like activity.

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. 

Histidine is characterized by a heterocyclic side chain known as imidazole. The imidazole group will bear a positive charge under physiological conditions. Histidine is the metabolic precursor to histamine, a potent inflammatory molecule. Antihistamines work by antagonizing the action of histamine. 

The principal pathways for the biogenesis and metabolism of histamine are well known. Histamine is formed by decarboxylation of the amino acid, L-histidine, a reaction catalyzed by the enzyme, histidine decarboxylase. This decarboxylase is found in both mammalian and non-mammalian species. The mammalian enzyme requires pyridoxal phosphate as a cofactor. The bacterial enzyme has a different pH optimum and utilizes pyruvate as a cofactor (26.27). 

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. 

Metabolism. Histamine-storing cells form histamine by decarboxylation of the amino acid histidine. Released histamine is degraded no reuptake system exists as for norepinephrine, dopamine, and serotonin. 

Tabor, H., 1954, Metabolic studies on histidine, histamine and related imidazoles, Pharmacol. Rev., 6 299iB43. 

According to Sue (SIO), blood poisoning during pregnancy placed a stress on the supply of pyridoxine by reason of excess protein metabolism. This fact, together with the presence of elevated amounts of histidine and histamine, inhibited the action of vitamin Bb, and caused excretion of large quantities of xanthurenic acid. 

Metabolism. Histamine is formed from the amino acid histidine and is inactivated largely by deamination and by methylation. In common with other local hormones, this process is extremely rapid. 

Histamine is a low-molecular-weight amine compound formed by decarboxylation of histidine and is stored in basophil and mast cell granules. The release of histamine from these cells is triggered by antigen cross-linking IgE bound to specific receptors on the surface membranes of mast cells and basophils. The tissue effects of histamine are evident within 1 to 2 minutes, but it is rapidly metabolized within 10 to 15 minutes. The major effects of histamine on target tissues include increased capillary permeability, contraction of bronchial and vascular smooth muscle, and hypersecretion of mucus glands. 

As is the case for most enzyme activities measured in vitro, there is some doubt whether the histidine decarboxylase activities determined as above in various organs truly reflect the contribution of these organs to histidine decarboxylation in the intact animal. In vivo measurements give an overall picture of histidine decarboxylation in the living animal, but they can give little indication of the contribution made by individual organs. Moreover, the interpretation of such measurements is rendered difficult by bacterial decarboxylation of histidine in the gut, by metabolic destruction of histamine, and by the release of histamine from storage sites. Nevertheless, such measurements have provided much useful information, and they are particularly suited to the study of the effectiveness of histidine decarboxylase inhibitors in intact animals. As with in vitro methods the in vivo measurements can, in theory, be made either on the carbon dioxide or on the histamine formed in the decarboxylation. 

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