Histamine catabolism

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). 

Low blood histamine levels are observed during pregnancy (Clemetson, 1980), a reflection of increased histamine catabolism by placental DAO (Bardsley et al.. 

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). 

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. 

Histamine is synthesized in tissues by decarboxylation of amino acid L-histidine, a process catalyzed by the pyridoxalphosphate-dependent enzyme L-histidinedecarboxylase. Histamine can enter the organism with food it also can be generated by bacteria of the gastrointestinal tract. However, these sources do not create additional reserves of histamine since exogenous histamine is easily catabolized in the organism. 

Histidine - Decarboxylation of histidine yields histamine (see here). In the stomach, histamine promotes secretion of hydrochloric acid and pepsin as digestion aids. Histamine is a potent vasodilator, released at sites of trauma, inflammation, or allergic reaction. Reddening of inflamed tissues is a result of local enlargement of blood capillaries. Antihistamines block binding of histamine to its receptors. Figure 21.23 shows that histidine is catabolized to glutamate. 

All NMBDs inhibit histamine-A/-methyl-transferase (HMT), the primary catabolic enzyme for histamine in humans (see Fig. 3.6). Inhibition is competitive with respect to the methyl donor and noncompetitive with respect to histamine. Six different NMBDs, alcuronium, pancuronium, d-mbocurarine, gallamine, succinylcholine, and decamethonium, inhibited enzyme activity in the concentration range 10 -10 M with alcuronium being the most potent inhibitor ( 50=2 x 10" M)... 

Figure 5-12. Acetylation and methylation of histamine. (Adapted from Schayer RW, Catabolism of histamine in vivo, in Roche e Silva M, ed Histamines and Anti-histamines. Handbook of Experimental Pharmacology. Berlin Springer, 1966, Vol XVIII/1,pp 672-683.)...

Diamine oxidase (DAO) is a highly active degradative enzyme of the polyamine metabolic pathways, catabolizes a variety of substrates including histamine and diamines, and is localized to the mature villus epithelial cells of rodent intestinal mucosa (Wolvekamp and de Bruin 1994 John-Baptiste et al. 2012). Although blood DAO activity level correlates with both DAO expression in the villi of the small intestinal mucosa and the severity of small intestinal mucosal lesions induced by anticancer drugs, DAO measurement is confounded by the fact that plasma levels rise markedly upon heparin stimulation prior to blood draws, with peak elevations between 30 and 60 min (Luk et al. 1980, 1981 Tsunooka et al. 2004). 

Shayer, R. W. Catabolism of histamine in vivo. Handbook of Experimental Pharmacology, 18 672, 1966. 

The catabolic fate of histamine is complex and can vary with the species. Two enzymes are primarily responsible for the catabolic process. (1) The histamin-ase which deaminates histamine is probably none other than diamine oxidase. In man and hogs, however, in addition to diamine oxidase (in the tissues) there is a monoamine oxidase (in the blood) which differs from intracellular monoamine oxidases. (2) The fate of histamine depends above all on imidazole-N-methyl-transferase. Methylation (in position 1) is the condition which permits the monoamine oxidases to intervene, especially in the central nervous system. The CNS contains some histamine and methylation must necessarily precede the action of monoamine oxidase or any other related enzyme. Outside the CNS, it is difficult to be specific about the individual rdles of tissue histaminase and methyltransferase. Both of these appear to be involved in the catabolism of exogenous histamine or of endogenous histamine released into the circulation, while methyltransferase is believed to act only on endogenous histamine... 

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