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

73

levels may elevate when norepineph-

rine levels elevate. Decreased function

of sulfotransferase (SULT) enzymes

may elevate normetanephrine and me-

tanephrine levels. SULTs are not found

in neurons. SULT activity has been

down-regulated in vitro by coffee com-

pounds, green tea polyphenols, quercitin

and resveratrol. SULT enzymes also con-

jugate a variety of xenobiotic chemicals

that may be inhaled or ingested during

environmental exposures. SULT1A3

converts norepinephrine to normeta-

nephrine and its activity is decreased in

liver disease.

Studies indicate that hypertensive

males with obstructive sleep apnea have

higher urinary normetanephrine levels.

Norepinephrine and normetanephrine

may elevate when catecholamine-secret-

ing tumors are present. See Adrenal and

paraganglia tumors for more informa-

tion. Excess norepinephrine and norme-

tanephrine symptoms may include:

Hypertension

Palpitations or arrhythmia

Anxiety or nervousness

Nausea and vomiting

Abdominal pain

Chest pain

Irritability

Pallor

Sweating

Weight loss

Hand tremor

Insomnia

Normetanephrine is usually present

in the urine in small fluctuating amounts

and may be increased during and shortly

after stress exposures. Medications that

inhibit the reuptake of norepinephrine

or serotonin may also elevate normeta-

nephrine levels.

Synthesis and Metabolism:

NMet-SO

4

MHPG-SO

4

VMA

Met-SO

4

MHPG-SO

4

VMA

Normetanephrine

Metanephrine

DPHG

Norepinephrine

Epinephrine

SULT1A3

SULT1A3

MAO-A+AR

COMT

SULT1A3

ADH

COMT

COMT

PNMT

D H

MAO-A

MAO-A

AR

AR

Once released, norepinephrine

is metabolized to normetanephrine.

Adrenomedullary chromaffin cells pos-

sess catechol-O-methyltransferase

(COMT) and the metabolism 25-40%

of norepinephrine in the adrenal medul-

la occurs before the neurotransmitter is

released. COMT requires a magnesium

cofactor. COMT is not found in sympa-

thetic nerves, but monoamine oxidase

A (MAO-A) is. Contrary to usual de-

pictions of catecholamine metabolism,

vanillylmandelic acid (VMA) is primari-

ly produced by oxidation of norepineph-

rine metabolite 3-methoxy-4-hydroxy-

phenylglycol (MHPG), and metabolized

by alcohol and aldehyde dehydroge-

nases. The presence of a beta-hydroxyl