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




levels of DOPAC have

been associated with several conditions.

Impairment in the central dopamine

pathways and metabolism has been sug-

gested as a factor in the pathogenesis of

restless leg syndrome (RLS). DOPAC

inhibits the fibrillation of a-synnucle-

in; the aggregation of alpha-synnuclein

is associated with an increased risk of

Parkinson’s disease and other neuro-

degenerative disorders. The inhibition

of a-synuclein induces oxidative stress.

In vitro studies indicate that exposure

to high levels of manganese decreas-

es DOPAC levels; manganese excess is

associated with Parkinson’s-like symp-

toms. In animal studies, fasting and in-

hibition of sympathetic nervous system

stimulation decreased DOPAC levels.

In rats, four days of fasting resulted in

decreased DOPAC levels in the stom-

ach and heart, and sympathectomy de-

creased DOPAC in plasma and muscle.

DOPAC levels may be decreased in pa-

tients with paroxysmal atrial fibrillation

(PAF). Dihydropteridine reductase defi-

ciency (the failure to regenerate tetrahy-

drobiopterin [BH4], an essential cofac-

tor for tyrosine hydroxylase), decreases

plasma DOPAC levels.

Decreased DOPAC may indicate

a functional deficiency in monoamine

oxidase A (MAO-A) or aldehyde dehy-

drogenase enzymes. Mutations or sin-

gle nucleotide polymorphisms (SNPs)

in MAO-A genes have been associated

with aggression, behavior disorders, al-

coholism and attention deficit hyperac-

tivity disorder (ADHD). MAO oxidiz-

es catecholamines and serotonin. MAO

also oxidizes amines from the diet and

environmental exposures. Amines are

widely used in industry and aromatic

amines are common in food. Patients

with MAO-B deficiency usually have

normal plasma DOPAC levels. Animal

studies indicate that selenium may im-

prove MAO enzyme function.

MAO and norepinephrine reuptake

inhibitors may decrease plasma DOPAC

levels. Metyrosine therapy, which de-

creases the activity of tyrosine hydrox-

ylase (TH), decreases dopamine and

may decrease DOPAC levels. TH may

also be downregulated by excess cate-

cholamines, oxidative stress, nitrosative

stress and thiolation (reactions with sul-

fur amino acids).


DOPAC may occur in do-


-hydroxylase (D

H) defi-

ciency, which results in failure to con-

vert dopamine to norepinephrine, and

leads to elevated plasma DOPAC lev-

els. Rat studies indicate that DOPAC

levels will increase during acute stress-

ors, but may decrease with prolonged

or chronic stress. Increases in L-3,4-

dihydroxyphenylalanine (L-DOPA)

and dopamine occur after feeding and

enter the bloodstream as either DOPAC

or dopamine sulfate (animal studies).

Administration of reserpine, (which in-

hibits vesicular uptake of dopamine and

increases tyrosine hydroxylase activity)

or similar compounds, has been shown

to increases plasma DOPAC levels in

animals. Forskolin also increases plasma

DOPAC levels in animals. Catachol-O-

methyl transferase (COMT) enzyme de-

ficiencies increase DOPAC and decrease

3-methoxytyramine (3-MT) levels.