Histamine formation

Schwartz, J.-C., Lampart, C. Rose, C. (1972). Histamine formation in rat brain in vivo effects of histidine loads. J. Neurochem. 19, 801-10. 

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. 

The effect of temperature on histamine formation has been the subject of many studies (Table 6.5). Different studies reported 100-fold variations in histamine concentrations in skipjack tuna allowed to spoil under similar conditions. Although the information in Table 6.5 contains substantial variation, it is obvious that longer storage times and higher temperatures seem to induce histamine production. Control of biogenic amine production by low temperatures (for example 0°C) is consistently observed. 

Arnold, S.H., Price, R.J., and Brown, W.D. (1980). Histamine formation by bacteria isolated from skipjack tuna, Katsuwonas pelamis. Bull. Jpn. Soc. Sci. Fish. 46, 991-995. 

Relationship of Bacterial Histidine Decarboxylase Production to Histamine Formation. Many studies have been completed with the objective of understanding factors such as storage time and temperature that influence production of histamine in fish. The majority of the investigations have considered only the histamine content of the product, and, consequently, only limited information is available concerning the relationship of histidine decarboxylase formation by the microflora to histamine build-up. 

Rapid enzyme and histamine formation occurred in the inoculated fillets stored at 24 and 30°C. (Table 2 and Table 3). Maximal histidine decarboxylase activity occurred after 12 h of storage at both temperatures and decreased threafter. Histamine levels reached 520 mg/100 g and 608 mg/100 g at 24 and 30°C after 24 h of storage. At 24°C, the free histidine content decreased to 279 mg/100 g. In the uninoculated fillets, histidine decarboxylase activity was somewhat higher than noted in fillets stored at 15 C however, histamine content remained low after 24 h at 24°C and 30°C. 

Skipjack contains the highest histidine levels reported among various tunas (20, 24) consequently, histamine formation in decomposed skipjack should be relatively high. 

Incubation Temperature. The effect of temperature, the most important external factor affecting histamine formation, has been studied in a number of scombroid fish and bacterial cultures (1 > 32-34). However, variations in types of fish, handling procedures, and test organisms have contributed to wide differences in the results reported. 

Figure 1 shows the extent of histamine formation in whole skipjack tuna at temperatures over the range of 15.6 C to 48.9 C. After incubation for 24 h, samples were taken from the anterior section of... 

Figure 1 also shows that histamine formation is negligible at about 50 C and below 20 C. However, when longer incubations were used, histamine was produced at low temperatures. For example, we found 16.9 mg per 100 g after 12 days at 10 C, 7.3 mg per 100 g after... 

Figure 1. Effect of incubation temperature on histamine formation in skipjack tuna.

The intestine is believed to be a major source of bacteria responsible for histamine formation in skipjack tuna (25). The higher level and rate of histamine formation in the anterior section are related to the location of the intestinal tract in the forward end of the fish. Postmortem disintegration of the intestine liberates its microbial contents into the visceral cavity and anterior muscle tissue. 

Bacterial Growth and Histamine Formation. The quantitative relationship between histamine formation and the microbial flora in skipjack tuna at 38 C is shown in Figure 3. At intervals during incubation samples were removed from the second section and assayed for histamine content and bacterial numbers. After 24 h the anaerobic bacterial count was 3.5 x 10 per g, and the histamine content was 297 mg per 100 g. Anaerobic counts were used to measure the microbial population because over 92% of the bacteria found in decomposed skipjack tuna were obligate or facultative anaerobes (Table I). 

Figure 3. Bacterial growth and histamine formation in skipjack tuna at 38 °C. Reproduced with permission from Ref. Copyright...

A number of studies have dealt with histamine formation at low temperatures in several fish and in bacterial cultures ( 3, 7 9 27,... 

Table III. Histamine Formation at 4 C by Whole Cell Suspensions of...

Histamine formation at 4°C was studied with resting cell suspensions of several histidine decarboxylating bacteria (Table III). Cells were harvested from cultures grown at 38°C in Trypticase soy broth (BBL, Cockeysville, MD.), suspended in 0.2 M phosphate buffer (pH 6.0) containing 0.1% histidine, and incubated anaerobically at 4°C for 21 days. After incubation, the cells were removed by filtration, and histamine was measured in the supernatant liquid. 

Of the two species capable of growing at low temperatures (Table II), histamine formation at 4°C was negligible with JP. morganii cells and moderate with K. pneumoniae. However, cells of jC. perfringens, which did not grow at low temperatures (Table II), were active producers of histamine at 4°C. 

FDA (Food and Drug Administration). (2001b). Scombrotoxin (histamine) formation. In "Fish and Fishery Products Hazards and Controls Guidance," 3rd ed., pp. 83-102. Center for Food Safety and Applied Nutrition, Office of Seafood, Washington, DC. 

A scheme illustrating the possible mechanisms by which N -methylhistamine produced by H.p. may influence parietal cell function is shown in Figure 3. This scheme clearly shows that N -methylhistamine produced by H.p. could change the regulation of acid secretion in two opposite ways its effect on histamine formation in the fundus could reduce acid secretion, whereas the effect on somatostatin in the antrum could induce hypergastrinemia and thus increase acid secretion One could speculate that the final effect of this bacterium on acid production would depend on its distribution in the stomach. 

Exchange of the nicotinamide moiety of NADP for nicotinic acid, forming NAADP. Early studies also showed that the enzyme can catalyze exchange of nicotinamide with a variety of other bases, including histamine. Formation of histamine adenine dinucleotide phosphate was thought to provide an alternative to amine oxidase for rapid inactivation of histamine. 

It is possible for a tissue to have a low or impaired histamine-forming capacity (HFG) and yet to have a high histamine content by virtue of its ability to store the amine. Thus in rats subjected to prolonged inhibition of histamine formation by means of a pyridoxal-deficient diet , the HFC in abdominal skin, tongue and lung was reduced to less than 10 per cent of normal without diminishing the histamine content. In the gastric mucosa,... 

Several substituted histidines Table 4.8) have been tested as inhibitors of the histidine decarboxylase of guinea-pig kidney . From a consideration of the potencies of the substances tested, it was suggested that increasing the acidity of the nitrogens of the imidazole ring tended to produce stronger inhibitors. Similar studies on the inhibition of histamine formation by compounds related to DOPA or 5-HTP Table 4.8) showed that a-methyl-DOPA and DOPA are good inhibitors only the L-form of a-methyl-DOPA is an effective inhibitor of n-amino acid decarboxylase . The... 

There is considerable doubt at present concerning the physiological significance of the non-specific histidine decarboxylase . Nevertheless, the possibility remains that some of the compounds which have been found to inhibit the formation of dopamine and 5-HT may also be useful inhibitors of histamine formation. Comparative potencies, in vitro andf vivo, of various substances as inhibitors of the non-specific decarboxylase with DOPA as substrate have been recorded in the literature . ... 

Activation of the inducible enzyme becomes detectable 0-5-1 hour after application of the stress, and it persists for periods which depend on the nature and intensity of the stimulus. Under exceptional circiunstances the high rate of induced histamine formatation may be sufficiently prolonged to result in the development of shock . On the other hand, when the degree of activation of histidine decarboxylase is inadequate, tissue damage may occur as has been observed in the kidneys of endotoxin-treated rabbits . If histamine produced by inducible histidine decarboxylase is indeed a mediator of the slow phase of inflammation , inhibitors of this enzyme might possess anti-inflammatory action. It is thus of considerable interest that the ability of one class of anti-inflammatory drugs, the acidic group, to inhibit specific histidine decarboxylase runs parallel to their clinical activity . 

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