Melatonin for Prevention and Treatment of Complications Associated with Chemotherapy and Radiotherapy: Implications for Cancer Stem Cell Differentiation
Paloma Tejero, Hernán Pinto in Aesthetic Treatments for the Oncology Patient, 2020
The synthesis of melatonin begins with the hydroxylation of tryptophan to 5-hydroxy-tryptophan (5HTP) by tryptophan-5-hydroxylase (TPOH). This product is subsequently decarboxylated to 5-hydroxy-L-tryptamine (serotonin or 5-HT) under the catalytic action of aromatic amino acid decarboxylase (AADC). Serotonin is then acetylated to N-acetylserotonin by arylalkylamine N-acetyltransferase (AANAT). Finally, N-acetylserotonin is methylated to melatonin by hydroxyindole-O-methyl transferase (HIOMT), now known as N-acetyl-serotonin methyltransferase (ASMT) [43], which is a melatonin synthesis rate-limiting enzyme inhibited by light [44]. Therefore, melatonin concentrations in serum, mainly originating from the pineal gland, follow a circadian pattern.
Melatonin: A “Guardian” of the Genome and Cellular Integrity for Prevention of Photocarcinogenesis
Andreia Ascenso, Sandra Simões, Helena Ribeiro in Carrier-Mediated Dermal Delivery, 2017
The melatonin-biosynthesis pathway in skin, similar to what happens in other organs, is divided into four stages (Fig. 2.2), initiated by the uptake of the essential amino acid L-tryptophan by pineal parenchymal cells [6,31,36]. After this, L-tryptophan is converted to another amino acid, 5-hydroxytryp- tophan due the action of tryptophan hydroxylase enzyme (TPH), which is dependent on (6R) 5,6,7,8-tetrahydrobiopterin (6-BH4) [37]. There are two isoforms of tryptophan hydroxylase identified as TPH1 and TPH2. The first one is expressed in many peripheral tissues, including the skin, whereas TPH2 is expressed predomi- nantly in the central nervous system [38]. Thus, TPH1 is the responsible enzyme for the production of melatonin at skin level [33]. The second step of melatonin synthesis involves the decarboxylation of 5-hydroxytryptophan to serotonin by the aromatic amino acid decarboxylase enzyme (AAD). In the third step, serotonin is acetylated to N-acetylserotonin by arylalkylamine N-acetyltransferase (AANAT). Further, it is methyl- ated to melatonin via hydroxyindole-0-methyltransferase (HIOMT).
Melatonin and Serotonin in Plant Morphogenesis and Development
Akula Ramakrishna, Victoria V. Roshchina in Neurotransmitters in Plants, 2018
Both melatonin and serotonin have also been shown to have diverse effects on early seedling germination and growth. These studies encompass both exogenous application and studies examining the modified growth patterns of transgenic rice, tomato, and Arabidopsis lines, which have knockouts or up-regulation of genes in the indoleamine biosynthetic pathway. For example, experiments using Micro-Tom tomatoes (overexpression of the last biosynthetic enzyme in melatonin biosynthesis, HIOMT, or its mammalian analog AANAT (arylalkylamine N-acetyltransferase), individuals were found to have a modified branching structure, suggesting a role for melatonin in mediating growth patterns. It is interesting, however, to note that although the authors also found decreased auxin content in these mutants, serotonin levels were not determined. Given serotonin has been found to have diverse effects on shoot production, it is possible that these mutants may be responding to decreased serotonin levels resulting from the accelerated conversion of serotonin (via NAS) to melatonin in tissues. In rice, which were transformed to overproduce TDC (the first step in the biosynthetic pathway), an 11 to 25-fold increase in serotonin was observed depending on tissue type. Although melatonin was not quantified in this study, increased serotonin content was associated with shorter plants, again suggesting a role in growth patterning (Kang et al. 2007b). Indeed, the importance of T5H was highlighted in another study in rice, which found that overexpression of T5H coupled with supplementation with tryptamine could increase serotonin content, and supplementation was associated with modified root growth patterns (Kang et al. 2007a).
Ocular and systemic melatonin and the influence of light exposure
Published in Clinical and Experimental Optometry, 2019
Melatonin (N‐acetyl‐5‐methoxytryptamine), an indolamine, is synthesised from the precursor tryptophan, which is converted to 5‐hydroxytryptophan and serotonin by tryptophan 5‐hydroxylase and L‐amino acid decarboxylase,1999 and then to N‐acetylserotonin and melatonin by hydroxyindole‐0‐methyltransferase (HIOMT) and arylalkylamine N‐acetyltransferase (AANAT).1967 AANAT and HIOMT are critical enzymatic mediators of melatonin synthesis, with AANAT being a major rate‐limiting step. Circulating melatonin is degraded through several pathways involving multiple enzymatic steps, being primarily metabolised in the liver, kidney, and central nervous system.2010 In humans, melatonin is rapidly metabolised in the liver by hepatic cytochrome P450,2001 with a half‐life of approximately 45–60-minutes,2005 allowing measures of circulating melatonin in plasma to accurately reflect its synthesis. Melatonin is soluble in lipids and transported in the blood via albumin binding.1981
Diurnal and circadian variations in indole contents in the goose pineal gland
Published in Chronobiology International, 2018
N. Ziółkowska, B. Lewczuk, M. Prusik
Indolamines such as serotonin and melatonin have multiple functions, including regulation of mood and appetite, and of circadian rhythms, such as the sleep–wake cycle (Jenkins et al. 2016; Simonneaux and Ribelayga 2003). These substances are synthesized in the pineal gland, and one of them, serotonin, is also widely produced in other parts of the brain and body tissues (Jenkins et al. 2016; Rawdon and Andrew 1994; Simonneaux and Ribelayga 2003). The precursor for synthesis of all pineal indolamines is tryptophan, which is hydroxylated in the mitochondria of pineal parenchymal cells to 5-hydroxytryptophan (5-HTRP) (Figure 1) (Simonneaux and Ribelayga 2003). 5-HTRP is decarboxylated by aromatic amino-acid decarboxylase (AADC) to serotonin. Serotonin is transformed into N-acetylserotonin (NAS) by arylalkylamine N-acetyltransferase (AA-NAT), and then NAS is methylated by N-acetylserotonin O-methyltransferase (ASMT) to form the main pineal hormone, melatonin. The transformation of serotonin to melatonin is not the only metabolic pathway involving serotonin. Some of this amine undergoes oxidative deamination to 5-hydroxyindole acetaldehyde (5-HIAL), an unstable compound, which is reduced to 5-hydroxytryptophol (5-HTOL) or dehydrogenated to 5-hydroxyindole acetic acid (5-HIAA). These 5-hydroxyindoles are then methylated to 5-methoxytryptophol (5-MTOL) and 5-methoxyindole acetic acid (5-MIAA), respectively. Another possible pathway of serotonin transformation is its direct methylation by ASMT to 5-methoxytryptamine (5-MTAM).
UV-C radiation during the pupal stage affects morphological changes of wings in Tribolium castaneum (Col; Tenebrionidae)
Published in International Journal of Radiation Biology, 2019
Jatuporn Tungjitwitayakul, Thippawan Yasanga, Nujira Tatun
Previous research has shown that UV-C radiation can influence the expression profiles of the stress-responsive genes of the maize weevil (Sitophilus zeamais Motchulsky), such as heat shock protein 70 (hsp70), heat shock protein cognate 70 (hsc70), and heat shock protein 90 (hsp90) (Tungjitwitayakul et al. 2016). In this study, there were various significant abnormal characteristics of the wings. Based on the reports of gene functional analysis, there are many genes involved in the formation of elytra, pigmentation, and hindwing folding, including the abrupt (ab), Arylalkylamine N-acetyltransferase 1, and resilin genes, respectively (Haas et al. 2000; Noh et al. 2016; Ravisankar et al. 2016). However, the effects of UV-C on these candidate genes in T. castaneum need to be examined in the future.
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