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of proteinogenic amino acids are known, while many transformations are related
to microbiota. There are also many trace amine derivatives derived from aromatic
decarboxylated amines. For example, dopamine-β-hydroxylase converts p-tyramine
into p-octopamine, while catechol-O-methyl transferase converts dopamine into 3methoxytyramine. The chemical diversity of aromatic trace amines is increased
further by methylation to form N-methylphenylethylamine, N-methyltyramine,
synephrine, and N-methyltryptamine [4] (Fig. 2).
The function of the trace amines remains largely unknown. Many trace amines are
proven or putatively proven to be endogenous neural active compounds. Three trace
amines, β-phenylethylamine, p-tyramine, and tryptamine, have been demonstrated
as neuron modulators, although their action is complex. High-affinity mammalian
receptors for the archetypal trace amines have been investigated for a long time, and
these turned out to be a family of G-protein-coupled receptors (GPCRs) named trace
amine-associated receptors (TAARs). Humans have six functional TAAR genes,
of which most are orphan receptors expressed in the olfactory system, except for
TAAR1. As the target of β-phenylethylamine and p-tyramine, TAAR1 plays a role in
NH 2
O
OH
phenylalanine
NH 2
HO
O
OH
tyrosine
OH
O
NH 2
HO
HO
L-DOPA
NH 2
HO
HO
dopamine
NH 2
phenylethylamine
NH 2
HO
p-tyramine
NH 2
HO
O
3-methoxytyramine
NH 2
HO
p-octopamine
OH
N
H
N
H
HO
N
H
HO
OH
N-methylphenylethylamine
N-methyltyramine
synephrine
PNMT
AADC
PAH/TH
TH
AADC
COMT
trace amines
primary amines
secondary amines
Fig. 2 Metabolism and generation of some archetypal trace amines