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

109

A decrease in the activity of tyrosine

hydroxylase (TH),whichmetabolizes ty-

rosine to L-3,4-dihydroxyphenylalanine

(L-DOPA), may elevate tyrosine levels

and decrease levels of dopamine and

norepinephrine. TH requires iron and

tetrahydrobiopterin (BH4) cofactors.

Mutation of tyrosine aminotransferase

(TAT) may elevate tyrosine levels in

plasma and urine (type II tyrosinemia);

it is possible that single nucleotide poly-

morphisms (SNPs) may also alter TAT

activity, research continues in this area.

TAT requires pyridoxal phosphate (B6)

and alpha-ketoglutarate as cofactors and

oxidative stress has been shown to lower

TAT activity (in vitro).

Elevated plasma tyrosine levels have

been associated with seizures or devel-

opmental delays. Tyrosine hydroxylase

(TH) deficiency is a group of rare inher-

ited disorders that presents early in life

in one of three forms:

dystonia

mildest form with onset from

1-6 years; usually presents with

lower limb dystonia (involuntary

muscle contractions) or difficulty

walking, symptoms may worsen

in the evening and improve in

morning after sleep

infantile Parkinsonism with

motor delays

severe form with onset from

3-12 months; motor milestones

are delayed, presents with truncal

hypotonia and Parkinson’s

symptoms

progressive infantile encephalopathy

most severe form with onset

before 6 months; presents with

delay in motor development,

truncal hypotonia, limb

hypertonia (rigid/spastic)

hyperreflexia, ptosis, intellectual

disability, lethargy (with sweating

and drooling) alternates with

irritability

Synthesis and metabolism:

Phenylalanine

DopamineSO

4

HVA

Tyrosine

Phenylethylamine

Tyramine

DOPAC

3-MT

L-DOPA

Dopamine

MAO-B

MAO-A/B

PAH

TH

COMT

COMT

CYPD2

D H

SULT1A3

AADC

MAO-A/B

ALDH

MAO-A/B

ALDH

AADC

AADC

Phenylalanine, an essential amino

acid is converted into tyrosine via the

enzyme phenylalanine hydroxylase; the

enzyme requires a tetrahydrobiopterin

(BH4) cofactor.Tyrosine is then convert-

ed into L-DOPA by tyrosine hydroxy-

lase (TH), which requires BH4 and an

iron cofactor. Tyrosine hydroxylase is lo-

cated in dopamine and norepinephrine

neurons in various brain areas. In the pe-

riphery, TH is found in the adrenal me-

dulla and in sympathetic ganglia (nerve

clusters). Animal studies indicate that

selenium deficient diets increase the ac-

tivity of tyrosine hydroxylase two-fold.

Selenium deficiency also decreased

the expression of glutathione peroxidase

and glutathione reductase; decreased ex-

pression of these enzymes may increase