Tyramine oxidase

This group of enzymes catalyzes the oxidation of amines. Amine oxidase [EC 1.4.3.4], a flavin-containing enzyme (also known as monoamine oxidase, tyramine oxidase, tyraminase, or adrenalin oxidase) catalyzes the reaction of an organic amine R—CH2—NH2) with dioxygen... 

Activity also was strongly dependent on the absolute configuration. The (1S,2S)-enantiomer of 60a was an excellent inhibitor of tyramine oxidase, whereas the (1f ,2R)-enantiomer was essentially devoid of activity. 

Inhibition of copper-containing tyramine oxidase by fluorinated 1-phenylcyclopropylamines (62a-e, 63a-e, 64) also was investigated. These compounds displayed relatively poor activity as inhibitors [130, 133] (Table 3). 

Table 3. IC50 values and inhibition type of 2-aryl-2-fluoro and 1-aryl-2-fluorocyclopropylamines for tyramine oxidase [130, 131, 133]... 

T.C. Rosen, S. Yoshida, R. Frdhiich, K.L. Kirk, G. Haufe, Fiuorinated phenyicyciopropyiamines. 2. Effects of aromatic ring substitution and of absolute configuration on inhibition of microbial tyramine oxidase, J. Med. Chem. 47 (2004) 5860-5871. 

The role of amine oxidase in the inactivation of sympathomimetic amines rests on a much firmer basis. The enzymatic oxidative deamination of tyramine was described first by Hare (87). Kohn (105) partially purified it but the enzyme is widely distributed in mammalian tissues (30,109), is cyanide insensitive (15), and has resisted isolation. The name monamine oxidase has been suggested for the enzyme (154) referred to in the literature as tyramine oxidase, adrenaline oxidase (40), and aliphatic amine oxidase (128). 

Monoamine oxidase. Tyramine oxidase. Tyraminase. Amine oxidase. 

Roh JH et al (2000) Purification, cloning, and three-dimensional structure prediction of Micrococcus luteus FAD-containing tyramine oxidase. Biochem Biophys Res Coimnun 268 293-297... 

Fig. 11 Cross-sensitivity to selected biogenic amines shown by amine-degrading enzyme biosensors. TAO tyramine oxidase, MAO monoamine oxidase, DAO diamino oxidase. Adapted from data in [43]...

Lange and Whitmann Monoamine oxidase, tyramine oxidase and diamine oxidase Voltammetric Histamine / 1 pmolkg Tyramine/ 1 pmol kg Putrescine/ 1 pmol kg Food products [43]... 

Normally, dietary tyramine is broken down in the gastrointestinal tract by MAO and is not absorbed. In the presence of MAOI, however, all of its potent sympathomimetic actions are seen. Other side effects of MAOI include excessive CNS stimulation, orthostatic hypotension, weight gain, and in rare cases hepatotoxicity. Because the monoamine oxidase inhibitors exhibit greater toxicity, yet no greater therapeutic response than other, newer agents, clinical use has been markedly curtailed. The primary use for MAOIs is in the treatment of atypical depressions, eg, those associated with increased appetite, phobic anxiety, hypersomnolence, and fatigues, but not melancholia (2). 

Ubiquitous mitochondrial monoamine oxidase [monoamine oxygen oxidoreductase (deaminating) (flavin-containing) EC 1.4.3.4 MAO] exists in two forms, namely type A and type B [ monoamine oxidase (MAO) A and B]. They are responsible for oxidative deamination of primary, secondary, and tertiary amines, including neurotransmitters, adrenaline, noradrenaline, dopamine (DA), and serotonin and vasoactive amines, such as tyramine and phenylethylamine. Their nonselec-tive and selective inhibitors ( selective MAO-A and -B inhibitors) are employed for the treatment of depressive illness and Parkinson s disease (PD). 

Trace Amines. Figure 1 The main routes of trace amine metabolism. The trace amines (3-phenylethylamine (PEA), p-tyramine (TYR), octopamine (OCT) and tryptamine (TRP), highlighted by white shading, are each generated from their respective precursor amino acids by decarboxylation. They are rapidly metabolized by monoamine oxidase (MAO) to the pharmacologically inactive carboxylic acids. To a limited extent trace amines are also A/-methylated to the corresponding secondary amines which are believed to be pharmacologically active. Abbreviations AADC, aromatic amino acid decarboxylase DBH, dopamine b-hydroxylase NMT, nonspecific A/-methyltransferase PNMT, phenylethanolamine A/-methyltransferase TH, tyrosine hydroxylase. 

Pyridoxamine phosphate serves as a coenzyme of transaminases, e.g., lysyl oxidase (collagen biosynthesis), serine hydroxymethyl transferase (Cl-metabolism), S-aminolevulinate synthase (porphyrin biosynthesis), glycogen phosphoiylase (mobilization of glycogen), aspartate aminotransferase (transamination), alanine aminotransferase (transamination), kynureninase (biosynthesis of niacin), glutamate decarboxylase (biosynthesis of GABA), tyrosine decarboxylase (biosynthesis of tyramine), serine dehydratase ((3-elimination), cystathionine 3-synthase (metabolism of methionine), and cystathionine y-lyase (y-elimination). 

Benedetti, M, Boucher, T, Carlsson, A and Fowler, CJ (1983) Intestinal metabolism of tyramine by both forms of monoamine oxidase in the rat. Biochem. Pharmacol. 32 47-52. 

Escribano, J. et al., Characterization of monophenolase activity of table beet polyphenol oxidase determination of kinetic parameters on the tyramine/dopamine pair, J. Agric. Food Ghem., 45, 4209, 1997. 

Myelosuppression is the major side effect. Nausea, vomiting, and a flulike syndrome occur initially with therapy. Patients must be counseled to avoid tyramine-rich foods because procarbazine is a monoamine oxidase inhibitor. Patients should be provided a list of foods and beverages to avoid to prevent a hypertensive crisis. A disulhramlike reaction can occur with the ingestion of alcohol. 

MAOI (Monoamine Oxidase Inhibitors) will intensify and prolong the effects of NN-DMT, however this is never recommended. Foolish combinations of MAOIs and other drugs can lead to serious health problems and even death. The tryptamines are normally metabolized by an MAO in the body. MAO metabolizes serotonin, norepinephrine, and dopamine. By inhibiting this, MAOIs increase levels of those neurotransmitters. Tyramine will not be metabolized and will cause an increase in tyramine levels in blood. 

The natural ligand for the amine oxidase activity is not known for certain. While SSAO/VAP-1 will oxidize endogenous molecules such as methylamine and tyramine, the substrates associated with diapedesis are unknown. It has been speculated that leukocyte cell surface lysine residues or amino sugars, such as mannosamine residues (5) known to be associated with cell/cell recognition may be involved [14,15]. 

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. 

Hauptmann N, Grimsby J, Shih JC, Cadenas E. 1996. The metabolism of tyramine by monoamine oxidase A/B causes oxidative damage to mitochondrial DNA. Arch Biochem... 

Monoamine Oxidase inhibitors (MAOis). There are no controlled studies of MAOIs for the treatment of AN. In addition, the dietary restrictions imposed on patients taking this class of antidepressant and their propensity for lowering blood pressure makes their use in AN inadvisable. In the future, the issue of using MAOis may be reopened with the advent of the so-called reversible MAOis such as moclobemide that apparently do not require a tyramine-restricted diet. 

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