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

123

impair energy synthesis and use in the

CNS. The elevated levels of glycine in

the CNS result in intellectual disability,

poor muscle tone, chorea (involuntary

movements), respiratory or feeding diffi-

culties. Most cases are diagnosed during

infancy. Occasionally a patient will have

a milder, atypical form of disease, with

onset from late infancy into adulthood.

Glycine supplements may be used in

conjunction with pharmaceutical sup-

ports for schizophrenia or psychosis,

and may result in elevated urinary gly-

cine. Combinations of glycine with an-

tipsychotics or glycine transport inhibi-

tors have improved symptoms in some

schizophrenia patients, and increased

glycine serum levels have been reported

in schizophrenia patients responsive to

antipsychotics.

Synthesis and Metabolism:

³

³

³

³

³

³

³

³

³

³

Glycine

Serine

BHMT

Methionine

SAMe

CBS

SUOX

AHCY

MTR

MTHFR

SHMT

5, 10

Methylene THF

THF

dUMP

5 Methyl

THF

Homocysteine

Sulfate

Thymidine

synthesis

SHMT

SAH

TMG

DMG

methyltransferases

³

MTRR

³

Cystathionine

Cysteine

Sulfite

B12

Glycine is synthesized in the cell cy-

toplasm via serine hydroxymethyltrans-

ferase (cSHMT) using a pyridoxal phos-

phate (B6) cofactor. In the liver, glycine

may be synthesized using glycine syn-

thase and NADH. There is no specific

transporter across the blood-brain barri-

er (BBB) for glycine, but there are gly-

cine-specific transporters that take gly-

cine into cells and remove it from neural

synapses. There are two types of gly-

cine transporters, GLYT-1 and GLYT-2.

Mapping studies indicate that GLYT-1 is

primarily associated with astroglia cells,

and is found in the same CNS regions

as glycine receptors. GLYT-2 is primar-

ily associated with neurons. The glycine

transporters act as regulators of glycine,

which has dual functions: it acts as:

an inhibitory neurotransmitter at

glycinergic synapses and in the

spinal cord

as a modulator of neuron excitation,

mediated by NMDA receptors at

glutamate neuron synapses

The two major subtypes of glycine

transporters, GlyT1 and GlyT2, have

been linked to the pathogenesis and/

or treatment of central and peripher-

al nervous system disorders, including