Properties of mammalian tissue-bound semicarbazide-sensitive amine oxidase: possible clues to its physiological function?
ABSTRACT Semicarbazide-sensitive amine oxidase (SSAO), occurs not only in vascular smooth muscle but also in other cell types (e.g. adipocytes, chondrocytes, odontoblasts), probably in the plasma membrane. Although certain aromatic biogenic amines (e.g. tryptamine, tyramine, beta-phenyl-ethylamine) may be endogenous substrates for SSAO in species such as the rat, the weak activity of SSAO in human tissues towards these amines makes this less likely in man. However SSAO in human and rat vascular homogenates readily converts the aliphatic biogenic amines methylamine and aminoacetone to formaldehyde and methylglyoxal, respectively. Also the xenobiotic aliphatic amine allylamine produces cardiovascular damage in experimental animals by a mechanism which involves its deamination by SSAO to acrolein. Further metabolism of these toxic aliphatic aldehydes may involve glutathione-dependent pathways. Thus, SSAO may be involved not only in the removal of physiologically-active endogenous/xenobiotic amines, but resulting metabolite (aldehyde/H2O2?) formation could also influence cellular function.
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ABSTRACT: In contrast to early epidemiological evidence offering links between eosinophilia-myalgia syndrome (EMS) and microimpurities of L-tryptophan-containing dietary supplements (LTCDS), this account shows why reliance on a finite impurity from one manufacturer is both unnecessary and insufficient to explain the etiology of EMS. Excessive histamine activity has induced blood eosinophilia and myalgia (Greek: mys, muscle + algos, pain). Termination of the multiple actions of histamine is dependent on particular amine oxidases and histamine-N-methyltransferase. Histamine metabolism is rapid when these degradative reactions are operative. The latent effects of incurred histamine can be potentiated and aggravating when these mechanisms are impaired. Overloads of tryptophan supplements cause - among other relevant side-effects - an increased formation of formate and indolyl metabolites, several of which inhibit the degradation of histamine. Moreover, (non-EMS) subjects with hypothalamic-pituitary- adrenal (HPA) axis dysregulation have also manifested greatly increased sensitivities to incurred tryptophan and histamine. A final common pathway for syndromes characterized by eosinophilia with myalgia is now evident.Inflammation Research 12/2005; 54(11):435-50. · 1.96 Impact Factor
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ABSTRACT: The amine oxidases of mammalian tissues are a heterogeneous family of enzymes that metabolise various monoamines, diamines and polyamines produced endogenously, or being absorbed as dietary or xenobiotic substances. The heterogeneous class of amine oxidases can be divided on an arbitrary basis of the chemical nature of their cofactors into two types. Monoamine oxidase (MAO) and an intracellular form of polyamine oxidase (PAO) contain flavin adenine dinucleotide (FAD) as their cofactor, whereas a second group of amine oxidases without FAD contain a cofactor possessing one or more carbonyl groups, making them sensitive to inhibition by carbonyl reagents such as semicarbazide; this group includes semicarbazide-sensitive amine oxidase (SSAO) and the connective tissue enzyme, lysyl oxidase. This article focuses on the general aspects of MAO's contribution to the metabolism of foreign toxic substances including toxins and illegal drugs. Another main objective of this review is to discuss the properties of PAO and SSAO and their involvement in the metabolism of xenobiotics.Expert Opinion on Drug Metabolism & Toxicology 09/2006; 2(4):559-71. · 2.94 Impact Factor
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ABSTRACT: Trace amines, including tyramine, beta-phenylethylamine (beta-PEA), tryptamine and octopamine, are biologically active amines mostly based on phenylethylamine, occurring in the body in trace amounts. They are a diverse group of naturally occurring and synthetic amines, which are also found in the diet and in herbal plants, such as ephedrine and cathinone. They include amphetamine and its analogues, such as MDMA ('ecstasy'), and synthetic proprietary sympathomimetic agents such as phenylpropanolamine and pseudoephedrine. On the vascular system they cause vasoconstriction and a rise in blood pressure. This effect is the basis of their use as nasal decongestants. For over 50 years, they have been assumed to be indirectly acting sympathomimetic amines, their responses being due to the release of noradrenaline from sympathetic neurones. There are, however, results that suggest that this is not their only mechanism of action and that they may also exert direct vascular effects independent of a noradrenergic mechanism. Recently, a group of novel trace amine-associated receptors (TAARs) have been cloned and identified in the brain and peripheral tissues including blood vessels. Trace amines bind to these cloned receptors and it is suggested that their vasoconstrictor effects can in part be attributed to this mechanism. This review describes the cardiovascular pharmacology of this diverse group of amines, their structures and uses and their endogenous synthesis and metabolism. The review also considers their clinical relevance as constituents of the diet, as therapeutic agents (ritodrine, phenylpropanolamine, and pseudoephedrine) and as drugs of abuse (amphetamine, 'ecstasy') and their mechanisms of action.Pharmacology [?] Therapeutics 11/2009; 125(3):363-75. · 7.79 Impact Factor