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

7

There are two primary types of neu-

rotransmitter receptors,

ionotropic

and

metabotropic

. Ionotropic receptors open

or close channels in the cell membrane

to allow ions (such as calcium) to enter

or leave the cell. Changing the level of

ions in a cell affects the cell’s potential

to generate electrical signals (see Figure

3). Metabotropic receptors affect cell

activity indirectly through second mes-

sengers. Second messengers may have

local or systemic effects. Local second

messenger effects might involve changes

in nerve cell chemistry or DNA expres-

sion to make the cell more or less likely

to transmit information. Second mes-

senger pathways include the cyclic AMP

(adenosine monophosphate) pathway,

the inositol triphosphate/diacylglycerol

(IP3/DAG) pathway and the arachidon-

ic acid pathway.

The number, structure and function

of neurotransmitter receptors may be af-

fected by mutations or single nucleotide

polymorphisms (SNPs), which may al-

ter the amount of time a neurotransmit-

ter stays bound, and the ease of binding.

It is possible for neurotransmitter lev-

els to be normal, and still have symp-

toms, if the receptor is dysfunctional.

Neurotransmitter receptor defects have

been associated with mood disorders,

bipolar disorders, and addictive behav-

iors. Research continues to determine

how receptor dysfunctions might con-

tribute to neurodegenerative disorders

such as Alzheimer’s, Parkinson’s and

Huntington’s disease.

Neuro-biogenic Amine Synthesis

and Metabolism

Urinary neuro-biogenic amines pro-

vide an overall assessment of a patient’s

ability to synthesize and metabolize

neurotransmitters, which must occur in

both the peripheral nervous system and

behind the blood brain barrier (BBB)

in the central nervous system (CNS).

Altered patterns of urinary neuro-bio-

genic amines may highlight the need

for precursor amino acids or nutritional

cofactors essential for synthesis and me-

tabolism. The assimilation and absorp-

tion of nutrients requires a healthy di-

gestive tract and a healthy microbiome

(the presence of expected and beneficial

microbes in the gastrointestinal tract).

Neurotransmitters arise from amino

acid precursors (see Figure 4.)

Some neuro-biogenic amine precur-

sors are essential amino acids that must

be obtained from the diet. Other neu-

rotransmitters may be synthesized by

the body, and are considered non-essen-

tial. The essential amino acid precur-

sors are

phenylalanine

and

tryptophan

.

Mutations or single nucleotide poly-

morphisms (SNPs) may alter enzyme

conformation or function and affect

the synthesis of neuro-biogenic amines.

The enzymes in the synthesis pathway

require nutrient cofactors; the nutrients

will be reviewed in the specific informa-

tion for each neurotransmitter. However,

three important enzymes, phenylalanine

hydroxylase (PAH), tyrosine hydroxy-

lase (TH) and tryptophan hydroxylase

(TPH) begin the synthesis process. All

three enzymes require a tetrahydrobiop-

terin (BH4) cofactor, and all incorporate

iron into their structures. Defects in BH4

synthesis or recycling may affect neu-

rotransmitter synthesis and nitric oxide

signaling. BH4 deficiency may present

with elevated levels of precursor amino

acids and low levels of neurotransmit-

ters. Enzymatic defects in methylation

capacity (methionine metabolism and

transsulfuration pathways), may affect

BH4 levels and may increase oxidative

stress in the CNS. Oxidative stress may