China
Africa
Explore chapters and articles related to this topic
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.
Seasons and Photoperiodism
Published in Sue Binkley, Biological Clocks, 2020
Melatonin production is controlled by two enzymes. An indole molecule in the pineal gland, named serotonin (5-HT) is the precursor molecule. Using acetyl coenzyme A, the enzyme N-acetyltransferase (NAT) acetylates the serotonin producing N-acetylserotonin. The enzyme hyroxyindole-O-methyltransferase (HIOMT) uses S-adenosyl-methionine to methylate N-acetylsertonin producing melatonin.
Pineal Gland
Published in Paul V. Malven, Mammalian Neuroendocrinology, 2019
The primary secretory product of the pineal gland is melatonin and Figure 10-1 summarizes melatonin biosynthesis. Pinealocytes take up blood-borne tryptophan and convert it into 5-hydroxytryptophan using the enzyme tryptophan hydroxylase. The 5-hydroxytryptophan is then decarboxylated to yield the indolamine compound serotonin (also known as 5-hydroxytryptamine or 5-HT). Neither enzymatic conversion leading to the formation of serotonin is thought to be rate-limiting to biosynthesis of melatonin. However, the conversion of serotonin into N-acetylserotonin by the enzyme N-acetyltransferase (NAT) is a highly regulated and very rate-limiting reaction in melatonin synthesis. The final biosynthetic step involves the conversion of N-acetylserotonin to melatonin (also known as 5-methyoxy N-acetylserotonin) by the enzyme hydroxyindole-O-methyltransferase (abbreviated HIOMT). Most of the melatonin synthesized in pinealocytes is secreted into blood. A small portion is secreted into the cerebrospinal fluid (CSF) of the third ventricle, and some may be metabolized within the pinealocytes to biologically weaker compounds. Although the concentrations of melatonin in blood and in CSF are approximately equivalent, quantitative analysis of melatonin secretion by the sheep pineal gland revealed that far greater amounts were secreted into blood than into CSF, reflecting the much larger volume of blood compared to CSF (Rollag et al., 1978).
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].
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).
In vitro modulatory effects of ginsenoside compound K, 20(S)-protopanaxadiol and 20(S)-protopanaxatriol on uridine 5′-diphospho-glucuronosyltransferase activity and expression
Published in Xenobiotica, 2021
Su-Nyeong Jang, So-Young Park, Hyunyoung Lee, Hyojin Jeong, Ji-Hyeon Jeon, Im-Sook Song, Mi Jeong Kwon, Kwang-Hyeon Liu
Three ginsenoside metabolites (CK, PPD, and PPT) were screened for inhibitory activity against HLM UGT1A1, 1A3, 1A4, 1A6, 1A9, and 2B7 in comparison with schisandrin A, a known strong inhibitor of UGT1A3 (Liu et al. 2012). To obtain IC50 values, we used the substrate cocktail method which enables the cocktail incubation and estimation of compound inhibitory potential for six UGT isoforms (Joo et al., 2014). Each UGT isoform probe substrate was used at concentrations lower than their respective Michaelis-Menten constant (Km) values: 1.0, 0.5, 2.0, 1.0, 0.2, and 0.5 μM for naloxone (UGT2B7), SN-38 (UGT1A1), CDCA (UGT1A3), N-acetylserotonin (UGT1A6), mycophenolic acid (UGT1A9), and trifluoperazine (UGT1A4), respectively (Joo et al. 2014). In brief, HLMs (0.25 mg/mL) were diluted in the 0.1 M Tris buffer (pH 7.4) containing 10 mM magnesium chloride (MgCl2) and activated by incubation with 25 μg/mL alamethicin for 15 min on ice. After adding the UGT isoform-selective substrates and inhibitors (CK, PPD, PPT, and schisandrin A; 0, 2.5, 10, 25, 50, 100, and 200 μM), the mixtures were preincubated for 5 min at 37 °C. The reaction was initiated by adding UDPGA (5 mM) and incubated for 60 min. The reaction was terminated by adding cold acetonitrile (50 μL) containing 250 nM EG (Internal standard [IS]). After centrifugation for 10 min (14 000 g), aliquots of the supernatant were analysed by LC-MS/MS after filtration. The final organic solvent concentration was under 1.0% in each incubation mixture (Uchaipichat et al. 2004). Results were expressed as the means of triplicate experiments.