Benzylamine, deamination

There are two types of monoamine oxidase (i.e., A and B), which represent different proteins. MAO-A preferentially deaminates serotonin and NE, whereas MAO-B preferentially deaminates dopamine, benzylamine, and phenylethylamine. Certain substrates (e.g., tyramine and tryptamine) are comparably deaminated by both types. 

The enzyme found in the liver will deaminate secondary and tertiary aliphatic amines as well as primary amines, although the latter are the preferred substrates and are deaminated faster. Secondary and tertiary amines are preferentially dealky la ted to primary amines. For aromatic amines, such as benzylamine, electron-withdrawing substituents on the ring will increase the reaction rate. The product of the reaction is an aldehyde (Fig. 4.30). Amines such as amphetamine are not substrates, seemingly due to the presence of a methyl group on the a-carbon atom (Fig. 4.27). Monoamine oxidase is important in the metabolic activation and subsequent toxicity of allylamine (Fig. 4.31), which is highly toxic to the heart. The presence of the amine oxidase in heart tissue allows metabolism to the toxic metabolite, allyl aldehyde (Fig. 4.31). Another example is the metabolism of MPTP to a toxic metabolite by monoamine oxidase in the central nervous system, which is discussed in more detail in chapter 7. 

Deamination ofRNHI.t> A new method for reductive deamination of primary amines (1) involves conversion to an aromatic imidoyl chloride (2), which is converted to the hydrocarbon by Bu,SnH and AIBN (10, 412-413). Yields are satisfactory in the deamination of benzylamine, but are only moderate in the reaction of simple alkylamines. 

Deamination. The reagent can be used to effect deamination of a primary amine via the methanesulfonamide or an arylsulfonamide. For example, benzylamine... 

Kim, J.-M. Bogdan, M.A. and Mariano, P.S. Mechanistic analysis of the 3-methyllumiflavin-promoted oxidative deamination of benzylamine. A potential model for monoamine oxidase cdX2 y ,is. J Am Chem Soc 115 10591-10595, 1993. 

Above 250 °C, deamination of the reagent is observed and styrene is formed. Below this temperature, however, it is possible to obtain A-methyl-a-methylben-zylamine with good selectivity (90% selectivity at 20% conversion, 220 °C). The selectivity towards the N,N-dimethylated product is lower at the same conversion than with the other primary amine already tested, i. e. the -oetylamine (38 % at 84 % conversion for a-benzylamine and 57 % at 60 % conversion for n-octyla-mine). The NH group is bound to a secondary carbon in a-methylbenzylamine, whereas it is linked to a primary carbon in -octylamine. This steric factor explains the different reaetivity. This relatively good selectivity for monomethyla-tion can be regarded as an advantage compared with reductive alkylation. 

Histamlnase lyiamitte oxidase benzylamine oxj. dase histamine deaminase histamine oxidase E.C- 1.4,3,6. A copper contg enzyme present in tissues esp in kidneys and in the intestinal mucosa. Attacks diamines such as histamine in tbe body by oxidaiive deamination Best. J. Physiol 67, 256 (1929) Zeller Heiv. Chim. Acta 2l, 880 (1938) Advan. Entymol 2, 93 (1942). Extraction from hog kidneys Swedin. Acta Med. Scand. 114, 21 (1943). Identity with diamine oxidase Zeller Fed. Proc. 24, 764 (1965). Appears to have the general properties of a flavoprotein. Review E. A, Zeller "Diamine Oxidases in The Enzymes, vol. 8, P. D. Boyer et al, Eds. (Academic Press, New York 2nd ed., 1963) pp 313-335 Buffoni Pharmacol. Rev. ]8, 1163-1199 (1966) Hansson Scand- J. Clin. Lab, Invest, vol 31, suppl. 129 7 0973). 

Monoamine oxidase (MAO) is an enzyme present in the outer mitochondrial membrane of neuronal and non-neuronal cells. Two isoforms of MAO exist MAO-A and MAO-B. The MAO enzymes are responsible for the oxidative deamination of endogenous and xenobiotic amines, and have different substrate preferences, inhibitor specificities, and tissue distributions. MAO inhibition allows endogenous and exogenous substrates to accumulate, and may thereby alter the dynamics of regular monoamine transmitters, such as norepinephrine, serotonin, and dopamine. Specifically, MAO-A deaminates serotonin, norepinephrine, and dopamine, and MAO-B deaminates dopamine, [3-phenylethylamine, and benzylamine. In the human brain, about 75% of MAO is of the B subtype. Hence, the primary effect of MAO inhibitors (MAOIs) is to increase the availability of these neurotransmitters at the nerve terminal. 

Two isozymes, termed MAO A and MAO B, have been described. The early distinction between the two isozymes was based mainly on substrate selectivity and differential inhibition by various inhibitors . Serotonin and noradrenaline are preferentially deami-nated by MAO A, while benzylamine and phenylethylamine are better metabolized by MAO Dopamine and tyramine are equally deaminated by both isozymes. 

S-mono-oxygenase and the reduced enzyme requires the presence of additional reductant for hydroxylase activity. The deaminating enzyme benzylamine oxidase consists of two subunits and has two tightly bound, but well separated,... 

Monoamine oxidases (MAOs, EC 1.4.3.4) are a family of flavin-dependent metabolic enzymes that catalyze the oxidative deamination of biogenic and xenobi-otic amines. They play an important role in motor and mood control, as well as in the regulation of motivation and other brain functions. Two isoenzymes, MAO-A and -B, are distinguishable on the basis of their in vitro substrate specificity and inhibitor sensitivity [1]. MAO-A has a higher affinity for 5-HT, and to lesser extent, for noradrenaline and dopamine. It is inhibited by low concentrations of clorgyline, whereas MAO-B is more specific toward benzylamine, 2-phenylethylamine, and is inhibited by selegiline (Deprenyl) [2,3]. 

Most mammalian tissues display the presence of MAO-A and MAO-B isoforms with different substrate specificities. For example, MAO-A catalyses the oxidative deamination of serotonin, whereas MAO-B displays higher specificity for benzylamine and P-phenylethylamine. Noradrenaline, adrenaline, tyramine, tryptamine and dopamine are deaminated by both isozymes. In the human brain the hypothalamus and basal ganglia (striatum) show high MAO activity and it has been observed that... 

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