Tyramine production

Dacre, J. C. 1953. Cheddar cheese flavor and its relation to tyramine production by lactic acid bacteria. J. Dairy Res. 20, 217-223. 

Marcobal, A., Martin-Alvarez, P.J., Moreno-Arribas M.V, Munoz, R. (2006a). A multifactorial design for studying factors influencing growth and tyramine production of the lactic acid bacteria Lactobacillus brevis CECT 4669 and Enterococcus faecium BIFI-58. Res. Microbiol, 157, 417-424. 

Bunkova, L., Buhka, R, Drab, V, Kracmar, S., Kuban, V. (2012). Effects of NaCl, lactose and avaUabUity of oxygen on tyramine production by the Enterococcus durans CCDM 53. European Eood Research and Technology, 234, 973-979. http //dx.doi.org/ 10.1007/s00217-012-1714-y. 

Masson, R, Talon, R., Montel, M. C. (1996). Histamine and tyramine production by bacteria from meat products. International Journal of Food Microbiology, 32,199-207. 

Connil, N., Le Breton, Y., Dousset, X., Auffray, Y., Rince, A., Prevost, H. (2002). Identification of the Enterococcus faecalis tyrosine decarboxylase operon involved in tyramine production. Applied and Environmental Microbiology, 68, 3537-3544. http //dx.doi.Org/10.1128/AEM.68.7.3537-3544.2002. 

The main problems with early, irreversible MAOIs were adverse interactions with other drugs (notably sympathomimetics, such as ephedrine, phenylpropanolamine and tricyclic antidepressants) and the infamous "cheese reaction". The cheese reaction is a consequence of accumulation of the dietary and trace amine, tyramine, in noradrenergic neurons when MAO is inhibited. Tyramine, which is found in cheese and certain other foods (particularly fermented food products and dried meats), is normally metabolised by MAO in the gut wall and liver and so little ever reaches the systemic circulation. MAOIs, by inactivating this enzymic shield, enable tyramine to reach the bloodstream and eventually to be taken up by the monoamine transporters on serotonergic and noradrenergic neurons. Fike amphetamine, tyramine reduces the pH gradient across the vesicle membrane which, in turn, causes the vesicular transporter to fail. Transmitter that leaks out of the vesicles into the neuronal cytosol cannot be metabolised because... 

The discovery that MAO has two isoenzymes with different distributions, substrate specificity and inhibitor sensitivity has helped to rehabilitate the MAOIs to some extent. These isoenzymes are the products of different genes on the X-chromosome and share about 70% sequence homology. Whereas noradrenaline and 5-HT are metabolised preferentially by MAOa, tyramine and dopamine can be metabolised by either isoenzyme. Selective inhibitors of MAOa (e-g- moclobemide Da Prada et al. 1989) should therefore be safe and effective antidepressants whereas the selective MAOb inhibitor, selegiline, should not have any appreciable antidepressant activity (Table 20.5). 

Tyramine is an amino acid which is present in large quantities in protein rich, fermented and stored products like some cheeses, sausages, red wines, beers etcetera. Tyramine is metabolized into nor-adrenaline by the enzyme mono-amino-oxidase (MAO). If MAO is inhibited by drags nor-adrenaline is accumulated and can give hypertensive crises. 

Interlaboratory studies were carried out on the precision characteristics of the analytical methods used for determination of certain biogenic amines in fish and fish products, as required by German law. These included putrescine (4a), cadaverine (4b), tyramine (5) and histamine (6)78. 

Biogenic amines are commonly found in fermented meats. Histamine poisoning has not been associated with this type of product, however histamine has been found at low levels in some fermented meats (Dierick et al., 1974 Taylor et al., 1978 Vidal et al., 1990 Shalaby, 1993 Maijala et al., 1993). The most common amine found in fermented meats is tyramine (Trevino et al., 1997 Eerola et al., 1998), which is found at higher concentrations than other amines. The toxic level of biogenic amines is 100 mg per 100 g of product (Arnold et al., 1978). Taylor et al. (1978) and Vandekerckhove (1977) found amounts of histamine up to 55 mg per 100 g, putrescine up to 40 mg per 100 g, cadaverine up to 5.6 mg per 100 g, tyramine up to 151 mg per 100 g, and p-phenylethylamine up to 6.1 mg per 100 g in dry sausage. Table 6.9 lists the... 

Vidal, M.C., Izquierdo, M.L., Martin, M.C. and Marine, A. (1990). Histamine and tyramine in meat-products. Revista de Agroquimica y Tecnologia de Alimentos, 30, 102. 

The main limitation to the clinical use of the MAOIs is due to their interaction with amine-containing foods such as cheeses, red wine, beers (including non-alcoholic beers), fermented and processed meat products, yeast products, soya and some vegetables. Some proprietary medicines such as cold cures contain phenylpropanolamine, ephedrine, etc. and will also interact with MAOIs. Such an interaction (termed the "cheese effect"), is attributed to the dramatic rise in blood pressure due to the sudden release of noradrenaline from peripheral sympathetic terminals, an event due to the displacement of noradrenaline from its mtraneuronal vesicles by the primary amine (usually tyramine). Under normal circumstances, any dietary amines would be metabolized by MAO in the wall of the gastrointestinal tract, in the liver, platelets, etc. The occurrence of hypertensive crises, and occasionally strokes, therefore limited the use of the MAOIs, despite their proven clinical efficacy, to the treatment of atypical depression and occasionally panic disorder. 

The "cheese effect" is a well-established phenomenon whereby an amine-rich food is consumed while the patient is being treated with an irreversible MAOI. Foods which cause such an effect include cheeses, pickled fish, yeast products (red wines and beers, including non-alcoholic varieties), chocolate and pulses such as broad beans (which contain dopa). It appears that foods containing more than 10 mg of tyramine must be consumed in order to produce a significant rise in blood pressure. Furthermore, it is now apparent that there is considerable variation in the tyramine content of many of these foods even when they are produced by the same manufacturer. Therefore it is essential that all patients on MAOIs should be provided with a list of foods and drinks that should be avoided. 

MAO Inhibitors. MAO is an enzyme which oxidizes a variety of monoamines. Among the substrates of this enzyme are tyramine, tryptamine, 5-hydroxytryptamine, histamine, and short chain aliphatic monoamines ( ). Oxidation of histamine to imidazoleacetaldehyde can be carried out by DAO as well as MAO. is also responsible for the conversion of N -MH, the product of HMT, to N -MIAA. Many MAO inhibitors have been identified they are conventionally divided into hydrazides, hydrazines and amines (44). Some MAO inhibitors, e.g. the hydrazines, are non-selective they also inhibit DAO. 

One of the characteristics of intermedia is that in many cases it is not a stable compound (e.g., cadaverine). Intermedia is a compound which can be the final product of any pathway. However, an alkaloid can convert from an intermedia (e.g., norbelladine from tyramine in the galanthamine pathway), though this process is restricted. Generally, the synthesis pathway continues to establish the next compound, the obligatory intermedia. 

Avoid high-tyramine foods cheese (aged), sour cream, beer, wine, pickled products, liver, raisins, bananas, figs, avocados, meat tenderizers, chocolate,yogurt soy... 

Avoid tyramine-containing foods, beverages, and OTC products containing decongestants or dextromethorphan and products such as diet aids... 

Schoenfeld RC, Conova S, Rittschof D, Ganem B (2002) Cytotoxic, Antifouling Bromo-tyramines A Synthetic Study on Simple Marine Natural Products and Their Analogues. Bioorg Med Chem Lett 12 823... 

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