Tyramine, enzymic hydroxylation

Catecholamine neurotransmitters are subsequently inactivated by enzymic methylation of the 3-hydroxyl (via catechol-O-methyltransferase) or by oxidative removal of the amine group via monoamine oxidase. Monoamine oxidase inhibitors are sometimes used to treat depression, and these drugs cause an accumulation of amine neurotransmitters. Under such drug treatment, simple amines such as tyramine in cheese, beans, fish, and yeast extracts are also not metabolized and can cause dangerous potentiation of neurotransmitter activity. 

Dopamine /3-hydroxylase is a monoxygenase that catalyzes the hydroxylation of dopamine to form norepinephrine. This enzyme is localized in the chromaffin granules of the adrenal medulla and in the storage vesicles of central and peripheral catecholaminergic neurons. Since these compounds are unstable, this activity is often assayed by following the formation of octopamine from tyramine. For example, in the assay developed by Feilchenfeld et al. (1982), the reactant tyramine was separated from the product octopamine by reversed-phase, ion-paired HPLC (/uBondapak C18 using a mobile phase of 17% (v/v)... 

Octopamine is structurally very similar to norepinephrine being different only in lacking the 3-hydroxyl group on the aromatic ring (Figure 1). It may therefore be considered the monophenolic analogue of norepinephrine. In the vertebrate nervous system octopamine is synthesized by a decarboxylation of tyrosine to tyramine, and then by a subsequent 8-hydroxylation of tyramine (15). Whilst the enzymes have not been purified and characterized in insects a similar pathway appears to occur, since radiolabelled tyrosine and tyramine may be metabolized to octopamine by insect nervous tissue (3,16-17). 

The enzymes involved in the formation of the catecholamines are of low specificity. DOPA decarboxylase, or an enzyme closely akin to it, is concerned in the formation of 5-hydroxytryptamine > dopamine-/9-oxidase has been shown to be capable of hydroxylating the jd-carbon atom of a number of tyramine derivatives - and phenylethanolamine A-methyltransferase is equally unselective in its A-methylation of noradrenaline derivatives . This lack of specificity suggests the possibility that alternative pathways for the formation of noradrenaline and adrenaline might exist in vivo. Some of the putative intermediaries in these other pathways have been shown to occur naturally and one of them, octopamine (/) is found in the brain . 

Octopamine, a < -4 ml nomet by l)-4-hydroxy benz-enemethauol -taminomethyt1-p-hydroxybenzyt alcohol 1-(p-hydroxyphenyl)-2-aminoethanol norsympatol nor-synephrine p- hyd roxypheny let hanolam i ne WV 569. Cs -H N02 mo] wt 153.18. C 62.72%, H 7.24%, N 9.14%, O 20.89%. A biogenic amine that is the phenol analog of noradrenaline (norepinephrine, q.v,). It is a neurosecretory product found in several vertebrates and invertebrates. Formed by f)-hydroxylation of tyramine by the enzyme dopamine 0 -hydroxylase Pisano et a ., Btochlm. Biophys. 

It was found that, in addition to dopamine, the purified enzyme catalyzes the side chain hydroxylation of phenylethylamine and tyramine, while phenylalanine and ethylamine are not active (Levin and Kaufman, 1961). The side-chain hydroxylation of tyramine by adrenal slices has also been reported by Pisano et al. (1960). More recently (Bridgers and Kaufman, unpublished) epinine (iV-methyl-dopamine) has also been shown to be a substrate for the purified enzyme. 

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