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116

 Functional Assessment of Urinary Neuro-biogenic Amines—A COMPREHENSIVE GUIDE

Synthesis and Metabolism:

Phenylalanine

DopamineSO

4

HVA

Tyrosine

Phenylethylamine

Tyramine

DOPAC

3-MT

L-DOPA

Dopamine

MAO-B

MAO-A/B

PAH

TH

COMT

COMT

CYPD2

D H

SULT1A3

AADC

MAO-A/B

ALDH

MAO-A/B

ALDH

AADC

AADC

Trace amines derive from the aro-

matic amino acids (phenylalanine, tyro-

sine, tryptophan) through a decarboxyl-

ation reaction. This single-step process

is catalyzed by aromatic L-amino acid

decarboxylase (AADC), which requires

pyridoxal phosphate (vitamin B6) as a

cofactor. The action of AADC direct-

ly yields PEA from L-phenylalanine.

AADC activity is dependent on dopa-

mine levels, but not specific to dopa-

mine signaling. AADC activity may be

inhibited by autoimmune antibodies, or

lack of precursor amino acids may affect

PEA levels. PEA may not be stored; it

crosses cell membranes easily and may

act by local diffusion. Trace amines are

metabolized by monoamine oxidase

(MAO); PEA is primarily oxidized by

MAO-B to to phenylacetic acid. Animal

studies indicate that the addition of se-

lenium and tocopherols to the diet in-

creased antioxidant capacity and de-

creased MAO-B activity. Trace amines

and their metabolites are excreted by

the kidney in urine.

In vitro

studies indicate that PEA

may modulate dopamine, norepineph-

rine and serotonin monoamine trans-

porters and reuptake mechanisms. PEA

has been shown to depress gamma-ami-

nobutyric acid (GABA)-B receptor-me-

diated responses in dopamine neurons

(

in vitro

). PEA and tyramine may have

endocrine effects and inhibit prolactin

secretion (

in vitro

and

in vivo

). Animal

studies indicate that PEA may increase

adrenocorticotropic hormone (ACTH)

and glucocorticoid levels. PEA has also

been shown to stimulate acetylcholine

release through activation of glutamate

signaling pathways (

in vitro

). Levels of

PEA are not known to influence neuron

response to serotonin, GABA or gluta-

mate. Trace amines may activate sigma

receptors (

in vitro

), which modulate po-

tassium and calcium channels. Altering

the level of ions inside of neurons may

change their action potential and firing

rate.

Receptors:

The trace amine-associated recep-

tors (TAARs) are a recently discovered

class of receptors that respond to vari-

ous trace amines. Most TAARs activity

is the result of second messenger sig-

naling through cyclic adenosine mono-

phosphate (cAMP) and protein phos-

phorylation. TAARs are found in the

CNS and in the periphery are primarily

found in the gastrointestinal tract, lung,

and kidneys. In other mammals, some

TAARs may serve as olfactory chemore-

ceptors and may respond to stimulation

by odorous amines. Research continues

into the function of TAARs and their li-

gands as not all TAAR subtypes respond