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

41

sponse to changing conditions or neu-

ron activation. Epigenetic modifications

have been associated with neurodegen-

erative diseases such as Alzheimer’s dis-

ease and Huntington’s disease. Research

indicates that epigenetic modification

may also contribute to psychiatric dis-

orders, mood disorders and additive

behaviors.

One type of epigenetic DNA modi-

fication, methylation, attaches a methyl

group to the DNA strand. The methyl

group acts as an off switch, and prevents

the expression of the gene until it (the

methyl group) has been removed. If

there are too few methyl groups are at-

tached to DNA, then the mutation rate

of the DNA may increase. An increased

mutation rate has been associated with

increased cancer risk. If too many meth-

yl groups are attached to the DNA, then

the organism may lose the response flex-

ibility it needs to adapt to changing en-

vironmental conditions.

Methylation

The primary methyl group do-

nor molecule in the body is

S-adenosylmethionine (SAM). SAM is

produced during the metabolism (break-

down) of the essential amino acid me-

thionine (see Figure 11). Homocysteine,

the product of the methionine metabol-

ic pathway, is a necessary precursor for

another essential amino acid, cysteine,

which is synthesized in the trans-sulfu-

ration cycle. Glutathione (GSH) is the

primary antioxidant synthesized in the

body; it is synthesized from cysteine,

glycine and glutamate. Cysteine may

also be converted into taurine, another

amino acid essential for normal central

nervous system (CNS) function. The

synthesis of cysteine behind the blood

brain barrier (BBB), and its conversion

to GSH, is essential to prevent oxidative

stress and damage to the CNS.

SAM is the methyl donor in many

transmethylation reactions in the body,

including hormones, neurotransmitters,

DNA, RNA, and phospholipids. SAM is

the methyl donor used by the methyl-

transferase enzymes that synthesize neu-

rotransmitters (such as norepinephrine,

epinephrine, dopamine, serotonin, and

histamine). Normal SAM levels may be

required for the maintenance of myelin

(the fatty layer of insulation that sur-

rounds each nerve). Studies have shown

that SAMe supplements may help re-

verse demyelination. Studies also indi-

cate that SAMe oral supplements may

be effective in the treatment of depres-

sion. Animal studies have demonstrat-

ed increased levels of norepinephrine

and serotonin in the brains of rats giv-

en SAMe. SAM levels may also improve

cell membrane fluidity and some mem-

brane receptor functions. Other lines

of research implicate SAM deficiency

as contributing to the development of

Alzheimer’s disease.

The enzymes of methionine metab-

olism and the trans-sulfuration pathway

(commonly termed the “methylation

pathway”) are prone to inherited ge-

netic variation. Single nucleotide poly-

morphisms (SNPs) in the genetic code

for methylation pathway enzymes may

alter the enzyme’s structure and func-

tion. Many of the enzymes on the meth-

ylation pathway require nutritional co-

factors, such as B vitamins or minerals.

The methylation pathway is important

behind the blood brain barrier (BBB) to

provide cysteine, taurine and GSH to

neurons and glial cells.