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68

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

P h e n y l e t h a n o l a m i n e

N-methyltransferase (PNMT) cat-

alyzes the synthesis of epinephrine

from norepinephrine. PNMT requires

S-adenosyl methionine (SAM) as a co-

factor. Elevated norepinephrine and low

epinephrine levels may occur if PNMT

enzyme function is deficient. Serious

illness, physical activity or stress may

cause temporary increases in norepi-

nephrine and other catecholamines.

Pheochromocytoma tumors may secrete

norepinephrine.

Elevations in norepinephrine and

blood pressure may result in severe

throbbing headaches. Tyramine and oth-

er sympathomimetic amines, promote

the release of norepinephrine from

nerve endings. If monoamine oxidase a

(MAO-A) is inhibited by medication or

if enzyme function is deficient, tyramine

is able to reach the sympathetic nerve

terminals, and paroxysmal hypertension

may result from release of vesicular nor-

epinephrine. Short-term fasting (four

days) has been shown to elevate plasma

norepinephrine levels, as has the inges-

tion of glucose.

Synthesis and Metabolism:

Phenylalanine

HVA

NMet-SO

4

MHPG-SO

4

VMA

Met-SO

4

MHPG-SO

4

VMA

Tyrosine

Phenylethylamine

Normetanephrine

Metanephrine

Tyramine

DPHG

DOPAC

3-MT

Tryptamine

L-DOPA

Dopamine

Norepinephrine

Epinephrine

MAO-B

MAO-A/B

SULT1A3

SULT1A3

PAH

TH

MAO-A+AR

COMT

SULT1A3

ADH

COMT

COMT

COMT

COMT

CYPD2

PNMT

D H

AADC

MAO-A/B

ALDH

MAO-A/B

ALDH

MAO-A

MAO-A

AR

AR

AADC

AADC

AADC

Synthesis begins with the conversion

of tyrosine to 3,4-dihydroxyphenylal-

anine (L-DOPA) by the enzyme tyro-

sine-3-hydrolase (TH). Lack of nutrient

cofactors may decrease TH function; TH

requires tetrahydrobiopterin (BH4) and

iron for normal function. Tyrosine hy-

droxylase is located in dopamine and

norepinephrine neurons in various brain

areas. In the periphery, TH is found in

the adrenal medulla and in sympathetic

ganglia (nerve clusters). Animal studies

indicate that selenium deficient diets in-

crease the activity of tyrosine hydroxy-

lase two-fold. Selenium deficiency also

decreased the expression of glutathione

peroxidase and glutathione reductase;

decreased expression of these enzymes

may increase intracellular oxidative

stress. TH enzyme function may be

downregulated by oxidative stress, ni-

trosative stress and thiolation (reactions

with sulfur amino acids). Single nucleo-

tide polymorphisms (SNPs) in the genes

coding for tyrosine hydroxylase have

been associated with altered stress re-

sponses, blood pressure, heart rate and

norepinephrine secretion.

Dopamine is an intermediate me-

tabolite in the synthesis of norepi-

nephrine; L-DOPA is converted to