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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
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).
The melatonin receptor 1B gene links circadian rhythms and type 2 diabetes mellitus: an evolutionary story
Published in Annals of Medicine, 2023
Hui Zhu, Zhi-jia Zhao, Hong-yi Liu, Jie Cai, Qin-kang Lu, Lin-dan Ji, Jin Xu
Synthesis of the pineal hormone melatonin is regulated by the SCN master clock and synchronized to the environmental light-dark cycle. Melatonin secretion generally occurs in darkness (at night) and peaks at 00:00 and 4:00 am. Importantly, nighttime melatonin production is blocked by light, especially blue light at wavelengths of 460–480 nm and intensities < 200 lux [43–45]. The biosynthetic precursor of melatonin is tryptophan, which is hydroxylated to 5-hydroxytryptophan and then decarboxylated to generate serotonin. Subsequently, serotonin is acetylated to N-acetylserotonin by arylalkylamine N-acetyltransferase (AANAT) and then converted to melatonin by acetylserotonin O-methyltransferase [16]. When the environmental photoperiodic information reaches intrinsic photosensitive retinal ganglion cells (ipRGCs), it is conveyed to the SCN by the retinal hypothalamic tract. Afterward, the signal is projected to the pineal gland through a neuronal signaling cascade that promotes or inhibits melatonin secretion in pinealocytes (Figure 1) [41,46,47].
Circadian rhythms in diabetic retinopathy: an overview of pathogenesis and investigational drugs
Published in Expert Opinion on Investigational Drugs, 2020
Ashay D. Bhatwadekar, Varun Rameswara
The neural retina communicates photic information to other neuronal structures via humoral signals involving melatonin and dopamine. Melatonin displays a clear circadian rhythm both in vivo and in vitro and its rhythm is one of the most well studied circadian rhythms in the retina [26]. The retinal melatonin synthesis primarily occurs in the photoreceptors. Arylalkylamine N-acetyltransferase (AANAT) is a key regulatory enzyme in melatonin biosynthesis and is shown to exhibit rhythm in constant darkness as well as in SCN lesioned animals suggesting that the retinal clock is independent of the SCN [27]. The AANAT transcription is tightly regulated by clock and Bmal clock genes via binding to the E-box [28]. ipRGCs are most sensitive to short-wavelength light (~460-480 nm; blue) and can thereby control phase-shift. This effect of blue light on the circadian rhythm is observed in terms of melatonin response by functional ipRGCs. In blind subjects with no conscious perception of light, there was a melatonin suppression in response to blue light (460 nm), however no suppression was detected in response to green light (555 nm), suggesting the important role of blue light in regulating the melatonin response [29,30].
The pharmacotherapeutic management of postoperative delirium: an expert update
Published in Expert Opinion on Pharmacotherapy, 2020
In addition to neurotransmitter imbalance affecting network connectivity, stress in the form of sleep disturbance and circadian rhythm dysfunction is common in the setting of illness and surgery. Critical in the maintenance of circadian rhythm and promoting natural sleep initiation is the neuro-hormone melatonin which is produced from serotonin via its precursor the amino acid tryptophan in the pineal gland with its production controlled by the suprachiasmatic nucleus (SCN) in the hypothalamus. Melatonin is suppressed by light but when darkness falls, the SCN signals the pineal gland to release the neurotransmitter norepinephrine which binds to adrenergic beta receptors. Then in a series of steps, this leads to the synthesis of the enzyme arylalkylamine N-acetyltransferase and the production of melatonin which binds to two receptors (MT1 and MT2), where the former is related to sleep induction while the latter is involved in sleep – wake cycle regulation [60]. It is of note that melatonin may also have anti–inflammatory benefits and may reduce oxidative stress and preserve membrane fluidity [61] so for all of these reasons use of melatonin and its related compounds provide a sound rationale to address POD.