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Melatonin for Prevention and Treatment of Complications Associated with Chemotherapy and Radiotherapy: Implications for Cancer Stem Cell Differentiation
Published in Paloma Tejero, Hernán Pinto, Aesthetic Treatments for the Oncology Patient, 2020
Germaine Escames, Ana Guerra-Librero, Dario Acuña-Castroviejo, Javier Florido, Laura Martinez-Ruiz, Cesar Rodríguez-Santana, Beatriz I Fernandez-Gil, Iryna Russanova
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.
Roles of Melatonin in Maintaining Mitochondrial Welfare
Published in Shamim I. Ahmad, Handbook of Mitochondrial Dysfunction, 2019
Feres José Mocayar Marón, Emiliano Diez, Russel J. Reiter, Walter Manucha
Melatonin synthesis and secretion were initially described in the pineal gland; its synthesis is regulated by the environmental light/dark cycle via the suprachiasmatic nucleus. The pineal gland is part of the photoneuroendocrine system, and acts as a transducer, converting afferent neurally-coded photic information into melatonin, the chemical expression of darkness5. The precursors of melatonin are the aromatic amino acid tryptophan and serotonin. The pineal parenchyma captures tryptophan; then it is hydroxylated and decarboxylated to serotonin. Serotonin is then N-acetylated by the enzyme aralkylamine N-acetyltransferase (AANAT), and finally, the product is converted into melatonin by the N-Acetylserotonin-O-methyltransferase (ASMT), also known as hydroxyindole-O-methyltransferase (HIOMT)6. Melatonin is not stored within the gland but quickly diffuses into the bloodstream and cerebrospinal fluid7.
Melatonin: A “Guardian” of the Genome and Cellular Integrity for Prevention of Photocarcinogenesis
Published in Andreia Ascenso, Sandra Simões, Helena Ribeiro, Carrier-Mediated Dermal Delivery, 2017
Patricia Manteigas, Andreia Ascenso
Moreover, Liu and Borjigin evaluated whether AANAT is a rate-limiting enzyme of melatonin biosynthesis using a genetic mutant rat model [41]. Their data demonstrated that melatonin levels were not influenced by AANAT activity neither NAS (product of the AANAT activity). In addition, these authors also found that melatonin synthesis was limited by the HIOMT activity rate, and the recent identification of missense mutations in HIOMT from patients who suffered from autism spectrum disorders also supports the idea that HIOMT is the rate-limiting enzyme in the melatonin production as these patients displayed lower levels of melatonin secretion [42].
Role of BMAL1 and CLOCK in regulating the secretion of melatonin in chick retina under monochromatic green light
Published in Chronobiology International, 2020
Jiang Bian, Zixu Wang, Yulan Dong, Jing Cao, Yaoxing Chen
It is generally accepted that AANAT is the key enzyme that regulates melatonin synthesis (Klein et al. 1997). But, melatonin level is not entirely determined by the activity of AANAT (the penultimate enzyme in the melatonin biosynthetic pathway). Hydroxyindole O-methyltransferase (HIOMT, the last enzyme in the melatonin biosynthetic pathway) also plays an important role in melatonin synthesis (Iuvone et al. 2005). Compared with the percent of the variation of cAanat levels, the variation of melatonin levels in the cBmal1 interference experiments was minor (Figure 6). Therefore, we speculate that HIOMT plays a role in restricting melatonin levels such that resulting melatonin levels do not change to the same extent as due to cAanat in Bmal1 interference experiments.
Effect of pinealectomy on the circadian clock of the chick retina under different monochromatic lights
Published in Chronobiology International, 2019
Jiang Bian, Zixu Wang, Yulan Dong, Jing Cao, Yaoxing Chen
Avian retina possess a self-sustained molecular clock (Bailey et al. 2004; Chaurasia et al. 2006; Chong et al. 2003; Singh et al. 2013; Toller et al. 2006). As the key regulatory enzyme in the melatonin biosynthetic pathway, the AANAT contains an E-box enhancer element (Chong et al. 2000), which can be activated by CLOCK/BMAL1 heterodimer and may provide a link from the circadian clock to AANAT transcription. In comprehensive analysis of the phases (Figure 4), the acrophase of melanopsin was in advance of positive-regulating clock gene cBmal1, the cBmal1 showed a phase advance of approximately 6–8 h relative to cAanat and retina melatonin, meanwhile, the acrophases of negative clock genes followed cAanat and melatonin. These results seem to indicate a regulatory relationship of melanopsin, clock genes and melatonin.
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