N-Acetylserotonin O-methyltransferase, also known as ASMT, is an enzyme which catalyzes the final reaction in melatonin biosynthesis: converting Normelatonin 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. The other enzyme which catalyzes this reaction is n-acetylserotonin-o-methyltransferase-like-protein.
In humans the ASMT enzyme is encoded by the pseudoautosomal ASMT gene. A copy exists near the endcaps of the short arms of both the X chromosome and the Y chromosome.
Structure and gene location
N-Acetylserotonin O-methyltransferase is an enzyme that is coded for by genes located on the pseudoautosomal region of the X and Y chromosome, and is most abundantly found in the pineal gland and retina of humans. The structure of N- Acetylserotonin O-methyltransferase has been determined by X-ray diffraction.
Class of enzyme and function
N-Acetylserotonin O-methyltransferase can be classified under three types of enzyme functional groups: transferases, one-carbon group transferrers, and methyltransferases.
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.
Synonyms
Synonyms of N- Acetylserotonin O-methyltransferase are Hydroxyindole O-methyltransferase (HIOMT), Acetylserotonin O-methyltransferase (ASMT), Acetylserotonin N-methyltransferase, Acetylserotonin methyltransferase (Y chromosome). 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).
Amino acid sequences
Bos taurus (cattle) has 350 amino acids and the amino acid sequence is:
MCSQEGEGYSLLKEYANAFMVSQVLFAACELGVFELLAEALEPLDSAAVSSHLGSSPGD
RAATEHLCVPEAAASRREGRKSCVCKHGARQHLPGERQPQVPAGHAAVRGQDRLRLLAP
PGEAVREGRNQYLKAFGIPSEELFSAIYRSEDERLQFMQGLQDVWRLEGATVLAAFDLS
PFPLICDLGGGSGALAKACVSLYPGCRAIVFDIPGVVQIAKRHFSASEDERISFHEGDF
FKDALPEADLYILARVLHDWTDAKCSHLLQRVYRACRTGGGILVIESLLDTDGRGPLTT
LLYSLNMLVQTEGRERTPGRSTARSVGPAASETCGDGGRGEPTMLSWPGNQACSV
For Homo sapiens (human) with 373 amino acids the sequence is:
MGSSEDQAYRLLNDYANGFMVSQVLFAACELGVFDLLAEAPGPLDVAAVAAGVRASAHG
TELLLDICVSLKLLKVETRGGKAFYRNTELSSDYLTTVSPTSQCSMLKYMGRTSYRCWG
HLADAVREGRNQYLETFGVPAEELFTAIYRSEGERLQFMQALQEVWSVNGRSVLTAFDL
SVFPLMCDLGGTRIKLETIILSKLSQGQKTKHRVFSLIGGAGALAKECMSLYPGCKITV
FDIPEVVWTAKQHFSFQEEEQIDFQEGDFFKDPLPEADLYILARVLHDWADGKCSHLLE
RIYHTCKPGGGILVIESLLDEDRRGPLLTQLYSLNMLVQTEGQERTPTHYHMLLSSAGF
RDFQFKKTGAIYDAILARK
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.
Expression in immune cells
Recent studies found messenger RNA (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 endocrine and nervous system functions. In other words, the gene may be expressed in various isoforms in different cells of the body.