http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17505466&query_hl=2&itool=pubmed_docsum

as well as the following study re neurodegenerative disorders and melatonin which includes Alzheimers:

Acetylserotonin O-methyltransferase

From Wikipedia, the free encyclopedia

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 2.1.1.4) ^[5]

Figure 1.  

 Synonyms

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).

Organisms

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 2.1.1.4 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

 Tumors

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

Categories: Protein pages needing a picture | Genes on chromosome X | Transferases