Betreff: ASMT reaction MELATONIN BIOSYNTHESIS.....Wikipedia 5 28 07
Datum: Mon, 28 May 2007 14:45:32 EDT

While data is complicated, many of the details of the "ASMT Gene study" are straightforward and relatively easy-to-understand particularly when considering the importance of melatonin levels as related to not only the need for proper sleep but the large numbers of persons who suffer from symptoms of depression and related maladies.
Add to the gene study, the study "Abnormal melatonin synthesis in autism spectrum disorders

as well as the following study re neurodegenerative disorders and melatonin which includes Alzheimers: ,    the "critical need" for "proper studies
re "close, chronic, prolonged nighttime EMF exposures" becomes abundantly clear.
Note also that info re ASMT Gene indicates it is found not only in bacteria but also in chickens, cows, monkeys and rats as well as humans.  
Since symptoms lessened within two weeks of moving my grandsons beds away from elecric meters (appetite and less coughing -- followed by increases in overall IGG tests/"immune" several months later)   AND  surviving guinea pigs (one out of each set of two) also rapidly improved -- no more coughs followed by CBC's with differentials a month or so after moving them away from wall opposite electric meter, it is my opinion that guinea pig test results would most likely replicate very closely the changes that occur in humans.   I have other information -- "The Biology of Guinea Pig," that explains the adrenal glands in guinea pigs are larger than those of rats (more like adrenals in humans) and that they, like humans, produce cortisol rather than corticortoids.   Guinea pigs are considered to be quite radiosensitive as are many humans. 
Genetic testing is very costly.  White blood cell changes are "markers for irradiation" and are used to determine possible overexposure due to radiation treatments for cancer.  Since those "identical changes" have occurred in many persons as well as my two grandsons and my guinea pigs (two sets of two each), the sort of testing Assoc. Prof. Olle Johansson has agreed to do IF he receives the necessary funding, will be an important step toward slowing the progression of autism-like disorders, EOAD (Early Onset Alzheimers' Disease) as well as Childhood Leukaemia and most likely also Leukaemia and other cancers related to workplace exposures. 
Assoc. Prof. Olle Johansson also has considerable knowledge regarding the effects of UV exposure in regard to melatonin reduction.  In addition, he has suggested evaluation of histamine as an early marker re close, nighttime EMF/EMR exposure.  He has also mentioned the importance of evaluating chymase in regard to inflammation and cell signaling as well as other changes.  Certainly studies that include data re amylin are very important although it is possible that elevations in certain enzymes, etc. do not occur early on.   Once we get the necessary funding for Olle Johansson, he will know how many evaluations can be done in addition to white blood cells and melatonin.  I suspect "amount of funding" as well as "animal stress levels" will be the primary limiting factors.
Assoc. Prof. Olle Johansson's expertise lies in the fact that he has studied the effects of electromagnetic radiation/UV on the largest organ in one's body -- "the skin."   In addition to blood studies such as "white cell changes," the additional information regarding comparisons of histamine levels and other factors between studies already performed by Assoc. Prof. Olle Johansson and his colleagues re UV exposure with close, chronic, prolonged nighttime exposure (electric meters/appliances) that should also include evaluations of melatonin levels, will provide the answers needed to proceed with "common sense evaluations" regarding the more distant EMF/EMR expsosures.   [ See "Mystery in Skin" -- interview with Assoc. Prof. Olle Johansson:   .....]
I think the facts that are coming forward re "autism-like disorders" as opposed to "autism per se," plus also autisic-like findings in young adults, are highly significant.  The number of EOAD continues to climb.  I suspect many of those cases should more appropriately be called "Alzheimers-like Disorders."   We already know that my husband, Bud, who was diagnosed as having Alzheimers after years of declining neuropsych tests, has improved in three areas of his Executive Function and is now said not to have Alzheimers afterall....!!!!    I moved his electric clock radio off his nightstand and started him on melatonin.  He and I have both been taking four of the 3 milligram capsules (with no Vitamin B-6) every night before bed.  Bud no longer exhibits confabulation nor does he have delusions and nighttime agitation.   Bud is now 73 years old and had been having declining memory, increased agitation, cognitive dysfunction, etc. for over seven years.
The children await help from Dr. Johansson.    We need the support of the Alzheimers' Organization, foundations for autism, AARP (American Association for Retired Persons), the cancer societies, governments around-the-world and more -- in order to help Dr. Johansson help the children!!!!
The Charity "Children With Leukaemia" sanctioned a press release by Dr. Russel Reiter during the 2004 First International Children With Leukaemia Conference.  The press release indicated that "light at night may cause cancer....."    "The reason" this is so has to do with "reduced melatonin levels due to light......"
Children With Leukaemia is in an excellent position to create the excitement required to generate the necessary funds for Assoc. Prof. Olle Johansson to be "the leader that he is" and to tie-ends-together re the link between low levels of melatonin and all health problems and low level "chronic, prolonged EMF/EMR exposure.   Positive action by Children With Leukaemia will open doors to funding from other organizations and charities.  Assoc. Prof. Johansson and other leading EMF/EMR scientists from the UK will then be able to join forces with Assoc. Prof. Olle Johansson.    The results will be "astounding" -- health problems will diminish greatly and children will once again be able to study without "brain fog" due to sleeping close to electrical and telephone equipment at night.
In the meantime, WiFi and celluar antennae are placing concerns expressed above at an even higher level of urgency, hence the "critical need" for confirmatory studies re the close, nighttime EMF/EMR exposures. Similar problems re large numbers of persons using cell phones and other chronic, prolonged daytme occupational exposures.
We "need immediate action -- we and society, can't afford to wait....!!!     Prayers go out to all.....take care  -   Joanne
Joanne C. Mueller
Guinea Pigs R Us
731 - 123rd Avenue N.W.
Minneapolis, Minnesota  55448-2127 USA
Phone:   763-755-6114
Email:  (5-28-07)
All truth goes through three stages: first it is ridiculed:
then it is violently opposed: finally it is accepted as self evident.  - Schopenhauer
"No substance is a poison by itself. It is the dose that makes a substance a poison..."  Paracelsus (1493-1541)

"LIGHT" is at the end of the tunnel for all to see and the lights we are holding get brighter each day in spite of an occasional flicker......THEY are frantically running in circles -- THEY are running into themselves -- THEY WON'T WIN -- It sure is great to be on the side of TRUTH!!! ......  Joanne C. Mueller 1-17-06

Acetylserotonin O-methyltransferase

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N-Acetylserotonin O-methyltransferase is an enzyme that catalyzes the final reaction in melatonin biosynthesis, converting N-acetyl-serotonin to melatonin. This reaction is embedded in the more general tryptophan metabolism pathway. The enzyme also catalyzes a second reaction in tryptophan metabolism: the conversion of 5-hydroxy-indoleacetate to 5-methoxy-indoleacetate. [1]


 Structure and Gene Location

N- Acetylserotonin O-methyltransferase is an enzyme that is coded for by genes located on the PAR region of the X and Y chromosome, and is most abundantly found in the pineal gland and retina of humans. [2]

Although the exact structure of N- Acetylserotonin O-methyltransferase has yet to be determined by X-Ray diffraction, the crystal structure of the Maf domain of human N- Acetylserotonin O-methyltransferase-like protein has been found. [3]

 Class of Enzyme and Function

N- Acetylserotonin O-methyltransferase can be classified under three types of enzyme functional groups: transferases, one-carbon group transferers, and methyltransferases. [4] It catalyzes two reactions in the tryptophan metabolism pathway, and both can be traced back to serotonin. Serotonin has many fates in this pathway, and N- Acetylserotonin O-methyltransferase catalyzes reactions in two of these fates. The enzyme has been studied most for its catalysis of the final step of the pathway from serotonin to melatonin, but it also catalyzes one of the reactions in the many step process of serotonin → 5-Methoxy-indolacetate. Figure 1 is a clear picture of where N- Acetylserotonin O-methyltransferase is used during tryptophan metabolism (see two locations of enzyme number [5]

Figure 1.  


Synonyms of N- Acetylserotonin O-methyltransferase are Hydroxyindole O-methyltransferase (HIOMT), Acetylserotonin O-methyltransferase (ASMT), Acetylserotonin N-methyltransferase, Acetylserotonin methyltransferase (Y chromosome).[6] The most commonly used synonym is Hydroxyindole O-methyltransferase (HIOMT).


N- Acetylserotonin O-methyltransferase is found in both prokaryotes and eukaryotes. It is found in the bacteria Rhodopirellula baltica and Chromobacterium violaceum. It is also found in the following eukaryotes: Gallus gallus (chicken), Bos Taurus (cow), Homo sapiens (human), Macaca mulatta (rhesus monkey), and Rattus norvegicus (rat). [7]

 Amino Acid Sequences

[8] Bos taurus (350 Amino Acids)      [ Go to main link....for sequences ....]  

Alternative splicing

The human HOIMT gene is approximately 35 kb in length and contains 9-10 exons. The gene can be alternatively spliced to form at least three possible isoforms, although each of these isoforms has the same role in the biosynthesis of melatonin. It has also been found that the gene contains multiple promoter regions, an indication that multiple mechanisms of regulation exist. [9]

 Expression in immune cells

Recent studies found mRNA transcripts of the HOIMT gene in B lymphocytes, T helper lymphocytes, cytoxic T lymphocytes, and natural killer lymphocytes in humans. This finding, in conjunction with research on alternative splicing of the HOIMT hnRNA, suggests that Hydroxyindole O-methyltransferase (synonym for N- Acetylserotonin O-methyltransferase) plays a role in the human immune system, in addition to its endoctrine and nervous system functions. In other words, the gene may be expressed in various isoforms in different cells of the body. [10]

 Reactions catalyzed

In the tryptophan metabolism pathway, N- Acetylserotonin O-methyltransferase catalyzes two separate reactions. The first reaction shown (Figure 2) is the reaction of N-acetyl-serotonin to N-acetyl-5-methoxy-tryptamine. S-adenosyl-L-methionine is used as a substrate and is converted to S-adenosyl-L-homocysteine. [11]

Figure 2: Reaction catalyzed by N- Acetylserotonin O-methyltransferase

Figure 3 is the same reaction as above, but the figure provides a clearer picture of how the reactant proceeds to product using N-Acetylserotonin O-methyltransferase in addition to the substrate. [12]

Figure 3: Role of N- Acetylserotonin O-methyltransferase


The second reaction (Figure 4) catalyzed by N-Acetylserotonin O-methyltransferase in the tryptophan metabolism pathway is: S-Adenosyl-L-methionine + 5-Hydroxyindoleacetate ↔ S-Adenosyl-L-homocysteine + 5-Methoxyindoleacetate. [13]

Figure 4: Second reaction catalyzed by N- Acetylserotonin O-methyltransferase

Figure 5 is a more general scheme of the reaction pathway from serotonin to melatonin. The number refers to the Enzyme Commission Number (EC Number) for N- Acetylserotonin O-methyltransferase. These two steps are embedded in the highly involved tryptophan metabolism pathway. [14]

Figure 5: Pathway serotonin → melatonin

 Clinical implications


There is evidence of high HIOMT gene expression in pineal parenchymal tumors (PPTs). This finding has led to the study of varying gene expression as a diagnostic marker for such tumors. Abnormally high levels of HIOMT in these glands could serve as an indication of the existence of PPTs in the brain. [15]

 Psychiatric Disorders

Melatonin levels are used as a trait marker for mood disorders, meaning that abnormal levels of melatonin can be used in conjunction with other diagnostic criteria to determine whether a mood disorder (eg Seasonal affective disorder, bipolar disorder, or major depressive disorder) exists. Melatonin levels can also be used as a state marker, contributing to conclusions on the severity of a patient’s illness at a given point in time. Because studies have shown a direct correlation between the amount of hydroxyindole-O-methyltransferase in the pineal gland and the melatonin level, additional knowledge of HOIMT could provide valuable insight on the nature and onset of these impairing disorders. [16]

 Linkage analysis

High frequency polymorphism exists on the PAR region of the sex chromosomes, where the HIOMT gene is located. Linkage analysis of a diseased locus with high frequency polymorphism of this region could lead to vital information about the role of the this gene in genetic disorders. [17]

 Additional research

HIOMT as the limiting reagent in the melatonin biosynthetic pathway

There has been some controversy over the regulatory power of hydroxyindole-O-methyltransferase in the production of melatonin. In 2001, it was argued that another enzyme in the pathway, N-acetyl transferase (NAT) was the limiting reagent in the production of melatonin.[18] Recent findings, however, have suggested that HIOMT, not NAT, is the limiting reagent, and a direct correlation between HIOMT expression and melatonin levels has been shown to exist. [19]


^ Reiter, R.J., Tan, D., Terron, M.P., Flores, L.J. Melatonin and its metabolites: new findings regarding their production and their radical scavenging actions. Acta Biochemica Polonica. 2007 March:54(1):1-9.

[ Note:   There are 19 references.....only reference 19 above (Reiter, Tan et al is copied here....go to main link.....shown below all Wikipedia info.....jcm....5-28-07...]

 External links