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

65

intracellular oxidative stress. TH en-

zyme function may be down regulated

by oxidative stress, nitrosative stress and

thiolation (reactions with sulfur amino

acids). Single nucleotide polymorphisms

(SNPs) in the genes coding for tyrosine

hydroxylase have been associated with

altered stress responses, blood pressure,

heart rate and norepinephrine secretion.

L-DOPA is converted to dopa-

mine by amino acid decarboxylase

(AADC); the enzyme requires cop-

per and ascorbate (Vitamin C) co-

factors. Once released, dopamine is

methylated by catechol-O-methyl-

transferase (COMT). COMT uses

S-adenosyl-methionine (SAM) and a

magnesium cofactor to degrade dopa-

mine into 3-MT. 3-Methoxytyramine

is then further metabolized by mono-

amine oxidase A (MAO-A) and alde-

hyde dehydrogenase (ALDH) to ho-

movanillic acid (HVA). Pre-synaptic

uptake and metabolism of dopamine

give rise to 3,4-Dihydroxyphenylacetic

acid (DOPAC), a different metabolite.

Post-synaptic uptake and metabolism

produced both DOPAC and 3-MT.

Receptors:

3-Methoxytyramine binds with high

affinity to alpha-2A adrenergic recep-

tors, and with moderate affinity to al-

pha-2c1, D

1

and D

2

receptors.The bind-

ing of a catechaolamine to an adrenergic

receptor usually stimulates the sympa-

thetic nervous system. Experimental

inhibition of COMT reduces levels of

3-Methoxytyramine. As COMT is the

rate-limiting enzyme, SNPs or mutations

that affect COMT enzyme functions

may affect levels of 3-Methoxytyramine.

The inhibition of monoamine oxidase A

(MAO-A) may elevate both 3-MT and

normetanephrine levels.

Consider:

Essential precursor Amino Acid

status

( Plasma

or

Urine Amino Acids

)

Magnesium status

Selenium status

MAOA or COMT SNPs

( DNA Methylation Pathway )

Methionine metabolism and

methylation pathways

( Plasma Methylation Profile, DNA Methylation Pathway )

References:

Alachkar, Amal; Brotchie, Jonathan M.;

Jones, Owen T. (2010)

Binding of dopamine and 3-methoxy-

tyramine as l-DOPA metabolites to

human α2-adrenergic and dopaminergic

receptors

Neuroscience Research

vol. 67 (3) p. 245-249

Antkiewicz-Michaluk, Lucyna; Ossowska,

Krystyna; Romańska, Irena; Michaluk,

Jerzy; Vetulani, Jerzy (2008)

3-Methoxytyramine, an extraneuronal do-

pamine metabolite plays a physiological

role in the brain as an inhibitory regula-

tor of catecholaminergic activity

European Journal of Pharmacology

vol. 599

(1) p. 32-35

Booij, L; Van der Does, A J W; Riedel, W J

(2003)

Monoamine depletion in psychiatric and

healthy populations: review

Molecular Psychiatry

(2003) 8, 951–973.

doi

:10.1038/sj.mp

.4001423

Cabib, S.; Puglisi-Allegra, S. (1996)

Different effects of repeated stressful expe-

riences on mesocortical and mesolimbic

dopamine metabolism

Neuroscience

vol. 73 (2) p. 375-380