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72

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

Zauner, Christian; Schneeweiss, Bruno;

Kranz, Alexander; Madl, Christian;

Ratheiser, Klaus et al. (2000)

Resting energy expenditure in short-term

starvation is increased as a result of an

increase in serum norepinephrine

Am J Clin Nutr

vol. 71 (6) p. 1511-1515

Normetanephrine

Normetanephrine is a metabolite

of norepinephrine. The adrenal glands

are the single largest source of norme-

tanephrine. Between 25-40% of circu-

lating normetanephrine is derived from

catecholamine metabolism from the ad-

renal medulla. Both the catecholamines

and their metabolites are excreted in the

urine. In the normal population, plasma

metanephrine and normetanephrine

levels are low. Normetanephrine inhib-

its low affinity, high capacity biogenic

amine transporters such as organic cat-

ion transporters (OCTs) and the plas-

ma membrane monoamine transporter

(PMAT). These nonspecific transporters

are highly expressed in the brain, and

participate in the clearance of mono-

amine neurotransmitters from synapses

in to prevent neurotransmitter excess.

Clinically, normetanephrine provides an

index of norepinephrine released due to

sympathetic nerve activity.

Effects:

Decreased

levels of normetaneph-

rine may occur when norepinephrine

levels decrease. Low normetanephrine

levels may occur if catechol-O-meth-

yltransferase (COMT) function is defi-

cient. Pure autonomic failure is associ-

ated with low levels of norepinephrine

and normetanephrine. Rare, inherited

conditions such as dopamine beta-hy-

droxylase (D

H) deficiency and Menkes

disease may also decrease norepineph-

rine and normetanephrine levels. D

H

requires a copper cofactor. Multiple sin-

gle nucleotide polymorphisms (SNPs)

have been identified in the genes coding

for D

H and are being evaluated for as-

sociations in attention, behavior, psychi-

atric and neurodegenerative disorders.

Symptoms of norepinephrine insuffi-

ciency, which may be seen in D

H en-

zyme deficiencies, may include:

Cardiovascular disease

Severe orthostatic hypotension

Droopy eyelids

Stuffy nose

Reduced muscle tone

Recurring low blood sugar

Adrenaline deficiency

Ejaculation problems

Exercise intolerance

Metyrosine therapy decreases lev-

els of the precursor neurotransmitter

dopamine and may reduce norepi-

nephrine and normetanephrine levels.

Medications that may reduce norepi-

nephrine and normetanephrine levels

include anti-hypertensives (blood pres-

sure), serotonin reuptake inhibitors,

heart medications and lithium.

Excess

normetanephrine

may

occur if sulfotransferase (SULT) or

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

N-methyltransferase

(PNMT)

en-

zyme function is deficient. 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. Most cate-

cholamines are metabolized in the cells

that produce them; normetanephrine