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86

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

Men synthesize serotonin

faster, and with left/right brain

differences compared to females

Serotonin reactivity, when

experimentally induced in hand

veins, is greater in women than

men

Though reserves are similar in

men and women, women seem

to use up reserves more quickly

when stressed

Acute tryptophan depletion

results in a larger decrease in

serotonin synthesis in women

Migraine triggers may include

hormonal changes (peri-menstrual),

post-stress (“weekend” headache),

alcohol, pain and after intense

emotion/alarm/fear

Seasonal variation is seen in migraine

frequency; a study in an Artic

population reported peak migraine

frequency in January, and lowest

migraine frequency in June

Early evidence indicates that

the vitamin D response element

(VDRE), in combination

with vitamin D, increases the

expression of the synthesis

enzyme tryptophan hydroxylase

in the brain

Synthesis and Metabolism:

5-HIAA

Tryptophan

Tryptamine

5-HTP

Serotonin

MAO-A/B

TPH2

(brain)

AADC

MAO-A

ALDH

AADC

TPH1

(bodypinealgland)

Serotonin is synthesized from the

amino acid L-tryptophan in pre-syn-

aptic neurons. The enzyme tryptophan

hydroxylase (TPH) produces 5-hy-

droxytryptophan (5-HTP) which is con-

verted to serotonin by aromatic ami-

no acid decarboxylase (AADC), also

called 5-HTP decarboxylase. AADC is

pyridoxal-phosphate (B6) dependent.

Different forms of the TPH enzyme

are found in the brain and in the gas-

trointestinal system. Evidence indi-

cates that vitamin D upregulates the

expression of TPH2 in the brain and

inhibits the expression of TPH1 in

the periphery.

A specific sequence of DNA of

the vitamin D response element

(VDRE), which is located near vita-

min D-regulated genes, is involved in

vitamin D signaling. Once synthesized,

serotonin is either stored in neuron ves-

icles or metabolized by monoamine oxi-

dase A (MAO-A). Serotonin is unable to

cross the blood-brain barrier (BBB) and

must be synthesized both peripherally

and in the central nervous system. Most

peripheral production occurs in the

gastrointestinal (GI) enterochromaffin

cells. The gastrointestinal tract produc-

es about 80% of the body’s serotonin.

Serotonin released into the synapse is

taken back up into presynaptic neurons

by the serotonin transporter (SERT).

There may be multiple forms of SERT

(isoforms) in the body and nervous

system. Platelets take up 10% of plas-

ma Serotonin. High levels of serotonin

within the platelet cells is a consistent

finding in autistic patients. Low levels of

platelet serotonin have been associated