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64

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

3-Methoxytyramine (3-MT)

3-Methoxytyramine is the primary

extracellular metabolite of Dopamine

released fromneurons. Inmice, 3-MT has

been shown to induce behavior chang-

es by binding the trace amine associat-

ed receptor 1 (TAAR1). Experimental

effects of 3-Methoxytyramine include

3-MT-induced tremor, repetitive behav-

iors and changes in activity levels (ani-

mal studies).

Effects:

Decreased

levels of 3-MT may

downregulate norepinephrine metab-

olism, as animal studies indicate that

3-Methoxytyramine accelerates nor-

epinephrine metabolism. Experimental

inhibition

of

catechol-O-methyl-

transferase (COMT) reduces levels of

3-Methoxytyramine. Metyrosine ther-

apy decreases the activity of tyrosine

hydroxylase (TH) and will decrease

dopamine levels, which may reduce

3-MT levels. TH function may also be

downregulated by high levels of cate-

cholamines, oxidative stress, nitrosative

stress and thiolation (reactions with sul-

fur amino acids).

Excess

levels of 3-MT may acceler-

ate norepinephrine metabolism. Animal

studies indicate that 3-Methoxytyramine

levels may increase during acute stress-

ors, but may habituate to repeated

stressors within 10 days. The herbicide

Paraquat has been shown to increase

3-MT levels in rats. Deficiency or inhi-

bition of monoamine oxidase (MAO)

may elevate 3-MT levels. MAO may be

inhibited by cigarette smoke.

Elevations of 3-MT have been associ-

ated with a variety of brain and carcinoid

tumors. Elevated 3-MT levels may occur

in Dopamine-secreting pheochromocy-

tomas, and in paragangliomas. Increases

in 3-MT characterized 70% of pheo-

chromocytoma patients with SDHB and

SDHD mutations. In some paragangli-

oma cases, only 3-methoxytyramine is

elevated. Plasma levels should always

be used to confirm results if catachol-

amine-producing tumors are suspected.

Genetic testing should be considered

in all patients with paraganglioma, for

as many as 50% of paragangliomas are

hereditary.

Synthesis and Metabolism:

DopamineSO

4

HVA

Tyrosine

DOPAC

3-MT

L-DOPA

Dopamine

PAH

TH

COMT

COMT

CYPD2

D H

SULT1A3

AADC

MAO-A/B

ALDH

MAO-A/B

ALDH

AADC

AADC

Phenylalanine

Tyrosine hydroxylase (TH) converts

the precursor amino acid tyrosine into

L-DOPA. Tyrosine hydroxylase is lo-

cated in dopamine and norepinephrine

neurons in various brain areas. In the pe-

riphery, TH is found in the adrenal me-

dulla and in sympathetic ganglia (nerve

clusters). Animal studies indicate that

selenium deficient diets increase the ac-

tivity of tyrosine hydroxylase two-fold.

Selenium deficiency also decreased the

expression of glutathione peroxidase

and glutathione reductase; decreased ex-

pression of these enzymes may increase