Noradrenaline Tutorial


If one has a problem communicating with Noradrenaline (NA), they will feel fatigued. If you are fatigued, this could be you. An NA communication problem could be caused by clogged NA receptors or an NA deficiency. Deficiencies can be caused by problems in the synthesis of the NA. If you have a cake with 10 ingredients and one of them is missing, you are going to have trouble making that cake. Why would one be missing? Perhaps the transportation for that item to your kitchen counter had trouble, or something that is used to make that one ingredient was missing.

Noradrenaline Synthesis
There are several steps to NA synthesis, as summarized below:

1) Phenylalanine mixes with some enzymes (converts chemical to another chemical) and cofactors (more ingredients) to make Tyrosine. One can buy Tyrosine at the health food store to supplement.

2) Tyrosine mixes with some enzymes and cofactors to make Dopamine, a neurotransmitter itself.

3) Dopamine mixes with some enzymes and cofactors to make the Noradrenaline (NA) neurotransmitter.

4) Noradrenaline (NA) eventually dissolves by mixing with some enzymes and cofactors to make VMA, which can be measured in urine. If it is not seen here, one has a problem with one of the above steps.

We summarize below:

* Phenylalanine + enzyme + cofactors -> Tyrosine
* Tyrosine + enzyme + cofactors -> Dopamine
* Dopamine + enzyme (DBH) + cofactors -> Noradrenaline (NA)
* NA + enzyme + cofactors -> VMA

For the names of the enzymes and cofactors and details involving NA synthesis, click

Noradrenaline Problems
The following are things that can go wrong with the Noradrenaline system:

a) DBH is inactivated by lead, mercury, excess manganese, H2S (hydrogen sulfide synthesized during fermentation in small intestine by harmful bacteria and yeast), and sulfa-drugs (asthmatic inhalants, many antibiotics). Low DBH disrupts the synthesis of Dopamine, which disrupts the synthesis of NA.

b) One of the chemicals used to make NA is deficient.

c) Some the chemicals used to make NA are having trouble getting into the brain.

d) The NA receptor at the receiving nerve cell is blocked (e.g. due to a heavy metal molecule or excess sulfur toxins from impaired sulfoxidation). If this is the case, the VMA and NA levels may be normal, yet one still has a problem; and one would probably respond to an NA-Agonist drug that stimulates that specific blocked receptor.

e) Sulfides can impair the conversion of Dopamine to Noradrenaline if one has low levels of the protective Sulfite Oxidase enzyme. For more details on this important topic, please click

Idiopathic Hypersomnia = Neurological CFS

There is something called "idiopathic hypersomnia", which is daytime sleepiness. According to the International Classification of Sleep Disorders (ICSD), "idiopathic hypersomnia" is "a disorder of presumed central nervous system cause that is associated with a normal or prolonged major episode and excessive sleepiness...". Some believe this is related chemically to narcolepsy, which involves falling asleep during the day, involuntarily. One can learn more about "idiopathic hypersomnia" by clicking
here. Note that Modafinil (Provigil), the drug that stimulates the NA alpha-1 receptors (Did you do your brain reading?) has been found to be affective and safe with "idiopathic hypersomnia", as noted in REFERENCE #13.

Noradrenaline (NA) Synthesis

The noradrenaline (NA) neurotransmitter molecule is synthesized in the following steps. If there is a problem with one of these, NA levels will drop, neurological fatigue will ensue, and a NARI or NA-Agonists will probably pick one up.

Step #1 (Phenylalanine to Tyrosine Pathway)

+ Phenylalanine hydroxylase (enzyme, also called "phenylalanine-4-mono-oxygenase")
+ tetrahydrobiopterin (cofactor)
+ O2 (oxygen cofactor)

=== Converts into ===>

+ dihydrobiopterin
+ H2O (water)

Step #2 (Tyrosine to Dopa Pathway)

+ Tyrosinase (enzyme, also called "tyrosine hydroxylase")

=== Converts into ===>

Dihydroxyphenylalanine (also called "Dopa")

Step #3 (Dopa to Dopamine Pathway)

+ AAD (aromatic L-amino acid decarboxylase enzyme)

=== Converts into ===>

dopamine (also called "o-hydroxy-tyramine" and "dihydroxyphenylethylamine")

Step #4 (Dopamine to Noradrenaline Pathway)

+ Dopamine-Beta-Hydroxylase (enzyme, abbreviated "DBH")

=== Converts into ===>

Noradrenaline (major neurotransmitter in brain, abbreviated "NA")

Step #4 Side-Pathway Reactions

* dopamine + deaminase => Homoprotocatechuic acid
* Homoprotocatechuic acid + catechol-O-methyltransferase => Homovanillic acid (HVA)

Step #5 (Noradrenaline to Epinephrine Pathway)

+ Phenylethanolamine-N-methyltransferase (enzyme)

=== Converts into ===>


Step #6a (Epinephrine to Vanillic Aid Pathway)

i) Epinehrine + catechol-O-methyltransferase => metanephrine
ii) metaneprhrine + MAO => 3-Methoxy-4-hydroxymandelic aldehyde
iii) 3-Methoxy-4-hydroxymandelic aldehyde + Aldehyde Reductase => 3-Methoxy-4-hydroxyphenylglycol
iv) 3-Methoxy-4-hydroxyphenylglycol + aldehyde dehydrogenase => Vanillic acid ( not VMA )

Step #6b (Noradrenaline to Vanillic Acid Pathway)

i) Noradraneline + Catechol-O-Methyltransferase => normetanephrine
ii) Normetanephrine + MAO => 3-Methoxy-4-hydroxymandelic aldehyde
iii) 3-Methoxy-4-hydroxymandelic aldehyde + Aldehyde Reductase => 3-Methoxy-4-hydroxyphenylglycol
iv) 3-Methoxy-4-hydroxyphenylglycol + aldehyde dehydrogenase => Vanillic acid ( not VMA )

Step #6c (Noradrenaline to Vanilmandelic Acid Pathway)

i) Noradrenaline + MAO => 3,4 Dihydroxymandelic acid
ii) 3,4 Dihydroxymandelic acid + catechol-O-methyltransferase => Vanilmandelic Acid (VMA)


1) Words with "ase" on the end are enzymes, and these are used to convert one chemical to another.
2) The Catechol-O-methyltransferase enzyme is inhibited by P5P, and is supported by the cofactor SAMe, which means that SAMe deficiencies will inhibit this enzyme, and adding SAMe supplements may accelerate it's reactions.

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