Biogenic amines, including histamine, are formed in food by the action of microorganism decarboxylase enzymes from amino acid precursors. This event does not occur in natural or physiological amines, which are formed during metabolic processes of plants and animals.
Possibility of alternative biosynthetic routes and combined participation of different types of microorganisms and their possible interactions makes it more complicated to determine the exact responsibility of amine biogenesis in food.
Therefore, for histamine to grow in food specific requirements are needed:
1.Growth of micro-organisms with decarboxylase activity.
2.Availability of amino acid precursors and cofactors.
3.Favourable environmental conditions for synthesis and decarboxylases activity (pH, Aw, Tª…)
Metabolism of Food Histamine
Foods are complex and consist of nutrients that require to be degraded from the moment they enter the oral cavity. Digestive organs carry out the digestion of food thanks to digestive enzymes that reach the intestinal tract through several digestive secretions (salivary, gastric, pancreatic, intestinal and biliary) obtaining the nutrients required for the proper functioning of the organism.
Histamine, which is present in every food (of animal and plant origin), should be metabolized in order to be eliminated by urine without problems. Note that exogenous histamine does not have a functional role within the organism, and for this reason, it is eliminated without using any property.
There are two known main routes of histamine metabolism in living beings, where Histamine N-methyltransferase (HMT) and Diamine Oxidase (DAO) are implicated:
Degradation by Histamine-N-metyltransferase (HMT or HNMT)
HMT inactivates histamine by methylation of the imidazole ring forming N-methylhistamine, which becomes N-methylimidazole acetaldehyde by Monoamine Oxidase (MAO) and finally enzyme aldehyde dehydrogenase (ALDH) converts it in N-methylimidazole acetic acid.
HMT is an enzyme that degrades histamine in the liver tissue, but it is also present in lower quantity in other tissues. Many studies establish a small relation of HMT in histamine metabolism in intestinal mucosa, as its activity is almost insignificant compared to DAO activity.
It is a cytosolic protein and therefore, it can only convert histamine in the intracellular space of cells. This proves that its capacity to degrade histamine is lower than the Diamine Oxidase route, which has a role in inactivation and removal of extracellular histamine; and this confirms therefore that pathologies related to a high histamine concentration in blood, are associated with DAO deficiency and not with HMT.
Degradation via Diamine Oxidase (DAO)
In this route histamine suffers an oxidative deamination by DAO. The products are imidazole acetic acid and at the end, its riboside. Both metabolites of histamine route, the imidazole acetic acid and the N-methylimadazole acetic acid (of HMT route) have low activity and are removed by urine.
DAO is the most important enzyme that degrades histamine; but it is only located in some tissues; specifically in intestinal mucosa, kidneys, placenta, thymus and seminal vesicles. DAO also has little participation, not always, in the liver tissue. It is mainly located in intestinal epithelium, where it absorbs histamine (endogenous histamine too) and where DAO degrades it controlling the pass into portal blood. DAO located in liver controls the pass of histamine towards systemic circulation and when it is in the kidney, DAO degrades the reabsorbed histamine in the proximal tubule.
Diamine Oxidase is the main enzyme that degrades ingested histamine. Moreover, when DAO acts like a secretion protein, it can be responsible for waste collection after extracellular histamine is released and, therefore, tissues containing DAO are decisive in the systematic control of histamine bioavailability.
Diamine Oxidase is involved in other processes such as regulation of cellular division or differentiation in rapid proliferation tissues (bone marrow and intestinal mucosa), and can act as neurotropic link.
In pregnant females, DAO activity is higher than in not pregnant, from 500 to 1000 times higher. Placenta produces additional DAO amounts as a fetus-protection measure, ensuring correct histamine degradation.