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Acetylserotonin O-Methyltransferase

The Experts below are selected from a list of 159 Experts worldwide ranked by ideXlab platform

Jonas Melke – 1st expert on this subject based on the ideXlab platform

  • Mutation screening of melatonin-related genes in patients with autism spectrum disorders.
    BMC Medical Genomics, 2010
    Co-Authors: Lina Jonsson, Elin Ljunggren, Anna Bremer, Christin T. Pedersen, Mikael Landén, Kent Thuresson, Maibritt Giacobini, Jonas Melke

    Abstract:

    Background
    One consistent finding in autism spectrum disorders (ASD) is a decreased level of the pineal gland hormone melatonin and it has recently been demonstrated that this decrease to a large extent is due to low activity of the Acetylserotonin O-Methyltransferase (ASMT), the last enzyme in the melatonin synthesis pathway. Moreover, mutations in the ASMT gene have been identified, including a splice site mutation, that were associated with low ASMT activity and melatonin secretion, suggesting that the low ASMT activity observed in autism is, at least partly, due to variation within the ASMT gene.

  • Mutation screening of melatonin-related genes in patients with autism spectrum disorders
    BMC Medical Genomics, 2010
    Co-Authors: Lina Jonsson, Elin Ljunggren, Anna Bremer, Mikael Landén, Kent Thuresson, Maibritt Giacobini, Christin Pedersen, Jonas Melke

    Abstract:

    Background One consistent finding in autism spectrum disorders (ASD) is a decreased level of the pineal gland hormone melatonin and it has recently been demonstrated that this decrease to a large extent is due to low activity of the Acetylserotonin O-Methyltransferase (ASMT), the last enzyme in the melatonin synthesis pathway. Moreover, mutations in the ASMT gene have been identified, including a splice site mutation, that were associated with low ASMT activity and melatonin secretion, suggesting that the low ASMT activity observed in autism is, at least partly, due to variation within the ASMT gene. Methods In the present study, we have investigated all the genes involved in the melatonin pathway by mutation screening of AA-NAT (arylalkylamine N-acetyltransferase), ASMT, MTNR1A, MTNR1B (melatonin receptor 1A and 1B) and GPR50 (G protein-coupled receptor 50), encoding both synthesis enzymes and the three main receptors of melatonin, in 109 patients with autism spectrum disorders (ASD). A cohort of 188 subjects from the general population was used as a comparison group and was genotyped for the variants identified in the patient sample. Results Several rare variants were identified in patients with ASD, including the previously reported splice site mutation in ASMT (IVS5+2T>C). Of the variants affecting protein sequence, only the V124I in the MTNR1B gene was absent in our comparison group. However, mutations were found in upstream regulatory regions in three of the genes investigated, ASMT, MTNR1A , and MTNR1B . Conclusions Our report of another ASD patient carrying the splice site mutation IVS5+2T>C, in ASMT further supports an involvement of this gene in autism. Moreover, our results also suggest that other melatonin related genes might be interesting candidates for further investigation in the search for genes involved in autism spectrum disorders and related neurobehavioral phenotypes. However, further studies of the novel variants identified in this study are warranted to shed light on their potential role in the pathophysiology of these disorders.

Kyoungwhan Back – 2nd expert on this subject based on the ideXlab platform

  • Rice N-Acetylserotonin deacetylase regulates melatonin levels in transgenic rice
    Melatonin Research, 2020
    Co-Authors: Ok Jin Hwang, Kyoungwhan Back

    Abstract:

    A reverse melatonin biosynthetic pathway was recently discovered in plants, by which N-Acetylserotonin (NAS) is converted into serotonin by N-Acetylserotonin deacetylase (ASDAC) rather than into melatonin by N-Acetylserotonin O-Methyltransferase (ASMT). In this study, we generated transgenic rice plants in which ASDAC was either suppressed or overexpressed to determine whether ASDAC is functionally involved in melatonin biosynthesis. ASDAC-suppressed rice showed increased levels of NAS, 5-methoxytryptamine (5-MT), and melatonin, whereas ASDAC-overexpressed rice exhibited less melatonin synthesis than observed in the wild type. This finding is strong evidence of the role of ASDAC in melatonin biosynthesis in rice. The increased levels of 5-MT, which is produced either by ASDAC from melatonin or by serotonin O-Methyltransferase (SOMT) from serotonin in ASDAC-suppressed rice, was ascribed to enhanced SOMT enzyme activity rather than increased transcripts, such as ASMT or caffeic acid O-Methyltransferase (COMT) encoding SOMT activity.

  • Melatonin production in Escherichia coli by dual expression of serotonin N-acetyltransferase and caffeic acid O-Methyltransferase
    Applied Microbiology and Biotechnology, 2016
    Co-Authors: Yeong Byeon, Kyoungwhan Back

    Abstract:

    Melatonin is a well-known bioactive molecule produced in animals and plants and a well-studied natural compound. Two enzymatic steps are required for the biosynthesis of melatonin from serotonin. First, serotonin N -acetyltransferase (SNAT) catalyzes serotonin to N –Acetylserotonin (NAS) followed by the action of N –Acetylserotonin O -methyltransferase (ASMT), resulting in the synthesis of O -methylated NAS, also known as melatonin. Attempts to document melatonin production in Escherichia coli have been unsuccessful to date due to either low enzyme activity or inactive ASMT expression. Here, we employed caffeic acid O -methyltransferase (COMT) instead of ASMT, as COMT is a multifunctional enzyme that has ASMT activity as well. Among several combinations of dual expression cassettes, recombinant E. coli that expressed sheep SNAT with rice COMT produced a high quantity of melatonin, which was measured in a culture medium (1.46 mg/L in response to 1 m m serotonin). This level was several orders of magnitude higher than that produced in transgenic rice and tomato overexpressing sheep SNAT and ASMT , respectively. This heterologous expression system can be widely employed to screen various putative SNAT or ASMT genes from animals and plants as well as to overproduce melatonin in various useful microorganisms.

  • On the significance of an alternate pathway of melatonin synthesis via 5-methoxytryptamine: comparisons across species.
    Journal of Pineal Research, 2016
    Co-Authors: Rüdiger Hardeland, Kyoungwhan Back, Lucien C. Manchester, Moisés Alejandro Alatorre-jiménez, Russel J. Reiter

    Abstract:

    Melatonin is a phylogenetically ancient molecule. It is ubiquitously present in almost all organisms from primitive photosynthetic bacteria to humans. Its original primary function is presumable to be that of an antioxidant with other functions of this molecule having been acquired during evolution. The synthetic pathway of melatonin in vertebrates has been extensively studied. It is common knowledge that serotonin is acetylated to form N-Acetylserotonin by arylalkylamine N-acetyltransferase (AANAT) or arylamine N-acetyltransferase (SNAT or NAT) and N-Acetylserotonin is, subsequently, methylated to melatonin by N-Acetylserotonin O-Methyltransferase (ASMT; also known as hydroxyindole-O-Methyltransferase, HIOMT). This is referred to as a classic melatonin synthetic pathway. Based on new evidence, we feel that this classic melatonin pathway is not generally the prevailing route of melatonin production. An alternate pathway is known to exist, in which serotonin is first O-methylated to 5-methoxytryptamine (5-MT) and, thereafter, 5-MT is N-acetylated to melatonin. Here, we hypothesize that the alternate melatonin synthetic pathway may be more important in certain organisms and under certain conditions. Evidence strongly supports that this alternate pathway prevails in some plants, bacteria, and, perhaps, yeast and may also occur in animals.

Lina Jonsson – 3rd expert on this subject based on the ideXlab platform

  • Genetic studies of autism and autistic-like traits
    , 2015
    Co-Authors: Lina Jonsson

    Abstract:

    Autism spectrum disorder (ASD) is characterized by impairment in social interaction, language impairment and repetitive behavior with varying degrees of severity. ASD represents the lower end on a continuously distributed measure of autistic-like traits (ALTs). Although a strong genetic component has repeatedly been identified in ASD, the genetic cause of ASD is still unknown for the majority of ASD cases. One of the main interests in this thesis is the neurobiology of melatonin, this interest is based on findings indicating lower levels of melatonin in children with ASD. In our investigations of rare mutations in melatonin related genes in subjects with ASD, we identified a previously reported mutation that has been shown to decrease the activity of one of the enzymes involved in the melatonin synthesis: the Acetylserotonin O-Methyltransferase (ASMT) (paper I). In the analysis of five common variations in the ASMT gene in relation to ALTs in the general population we found association between a single nucleotide polymorphism and social interaction impairment in girls (paper II). To broaden the analysis of genetic influences on ALTs, we have performed association analyses between ALTs in the general population and common variation in genes previously found to be associated with ASD (RELN, CNTNAP2, SHANK3 and CDH9/10 region) (paper III). Although these regions have previously been suggested to be strong ASD candidate regions, our results do not suggest a major influence of the investigated common variations on ALTs. In the final paper, rare inherited genetic variations were investigated in a large family with autism and language disorders. In this study, we used several techniques, including whole exome sequencing and copy number variation analysis (paper IV). In the family, several rare genetic variations which may partly explain the genetic etiology for autism in this family were identified. We performed functional analyses for a mutation identified in the CYP11A1 gene, indicating a gain of function mutation. The CYP11A1 gene encodes the first enzyme in the steroid hormone biosynthesis, thus our results may be in line with previous findings that have shown an elevated prenatal steroidogenic activity in ASD. In conclusion, we have identified both common and rare genetic variation that may increase the genetic susceptibility for ASD. Our analyses have highlighted the importance of taking both rare and common genetic susceptibility factors, as well as different symptoms of the disorders, into account when elucidating the complex inheritance of ASDs.

  • Mutation screening of melatonin-related genes in patients with autism spectrum disorders.
    BMC Medical Genomics, 2010
    Co-Authors: Lina Jonsson, Elin Ljunggren, Anna Bremer, Christin T. Pedersen, Mikael Landén, Kent Thuresson, Maibritt Giacobini, Jonas Melke

    Abstract:

    Background
    One consistent finding in autism spectrum disorders (ASD) is a decreased level of the pineal gland hormone melatonin and it has recently been demonstrated that this decrease to a large extent is due to low activity of the Acetylserotonin O-Methyltransferase (ASMT), the last enzyme in the melatonin synthesis pathway. Moreover, mutations in the ASMT gene have been identified, including a splice site mutation, that were associated with low ASMT activity and melatonin secretion, suggesting that the low ASMT activity observed in autism is, at least partly, due to variation within the ASMT gene.

  • Mutation screening of melatonin-related genes in patients with autism spectrum disorders
    BMC Medical Genomics, 2010
    Co-Authors: Lina Jonsson, Elin Ljunggren, Anna Bremer, Mikael Landén, Kent Thuresson, Maibritt Giacobini, Christin Pedersen, Jonas Melke

    Abstract:

    Background One consistent finding in autism spectrum disorders (ASD) is a decreased level of the pineal gland hormone melatonin and it has recently been demonstrated that this decrease to a large extent is due to low activity of the Acetylserotonin O-Methyltransferase (ASMT), the last enzyme in the melatonin synthesis pathway. Moreover, mutations in the ASMT gene have been identified, including a splice site mutation, that were associated with low ASMT activity and melatonin secretion, suggesting that the low ASMT activity observed in autism is, at least partly, due to variation within the ASMT gene. Methods In the present study, we have investigated all the genes involved in the melatonin pathway by mutation screening of AA-NAT (arylalkylamine N-acetyltransferase), ASMT, MTNR1A, MTNR1B (melatonin receptor 1A and 1B) and GPR50 (G protein-coupled receptor 50), encoding both synthesis enzymes and the three main receptors of melatonin, in 109 patients with autism spectrum disorders (ASD). A cohort of 188 subjects from the general population was used as a comparison group and was genotyped for the variants identified in the patient sample. Results Several rare variants were identified in patients with ASD, including the previously reported splice site mutation in ASMT (IVS5+2T>C). Of the variants affecting protein sequence, only the V124I in the MTNR1B gene was absent in our comparison group. However, mutations were found in upstream regulatory regions in three of the genes investigated, ASMT, MTNR1A , and MTNR1B . Conclusions Our report of another ASD patient carrying the splice site mutation IVS5+2T>C, in ASMT further supports an involvement of this gene in autism. Moreover, our results also suggest that other melatonin related genes might be interesting candidates for further investigation in the search for genes involved in autism spectrum disorders and related neurobehavioral phenotypes. However, further studies of the novel variants identified in this study are warranted to shed light on their potential role in the pathophysiology of these disorders.