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Tryptophan metabolites, such as 5-hydroxytryptophan (5-HTP), serotonin, and melatonin, hold significant promise as supplements for managing various mood-related disorders, including depression and insomnia. However, their chemical production via chemical synthesis and phytochemical extraction presents drawbacks, such as the generation of toxic byproducts and low yields. In this study, we explore an alternative approach utilizing S. cerevisiae STG S101 for biosynthesis. Through a series of eleven experiments employing different combinations of tryptophan supplementation, Tween 20, and HEPES buffer, we investigated the production of these indolamines. The tryptophan metabolites were analyzed using liquid chromatography with tandem mass spectrometry (LC-MS/MS). Notably, setups replacing peptone in the YPD media with tryptophan (Run 3) and incorporating tryptophan along with 25 mM HEPES buffer (Run 4) demonstrated successful biosynthesis of 5-HTP and serotonin. The highest 5-HTP and serotonin concentrations were 58.9 ± 16.0 mg L−1 and 0.0650 ± 0.00211 mg L−1, respectively. Melatonin concentrations were undetected in all the setups. These findings underscore the potential of using probiotic yeast strains as a safer and conceivably more cost-effective alternative for indolamine synthesis. The utilization of probiotic strains presents a promising avenue, potentially offering scalability, sustainability, reduced environmental impact, and feasibility for large-scale production. [ABSTRACT FROM AUTHOR]

Coffee is one of the most popular beverages in the world. Therefore, this study analyzed 49 coffee samples of Arabica and Robusta species of different geographical origins and the treatment of beans including three degrees of roasting with the use of LC-MS/MS. This is the first study to present a comprehensive analysis of Kopi Luwak coffee brew metabolites in comparison to fully washed coffees and the drying post-harvest treatment of Arabica or Robusta coffee brews. Kopi Luwak showed higher levels of caffeine and theophylline in comparison to the analyzed washed and unwashed Arabica coffees, as well as a different proportion of caffeoylquinic isomers. There was no difference between Kopi Luwak and other Arabica coffees in terms of the concentration of vitamin B3, amines, and phenolic acids. This was confirmed in PCA. The steaming and roasting of beans as well as the addition of black beans influence the concentration of 4-CQA and the nicotinic, ferulic, and quinic acids content. [ABSTRACT FROM AUTHOR]

Coffee is one of the most popular beverages in the world. Therefore, this study analyzed 49 coffee samples of Arabica and Robusta species of different geographical origins and the treatment of beans including three degrees of roasting with the use of LC-MS/MS. This is the first study to present a comprehensive analysis of Kopi Luwak coffee brew metabolites in comparison to fully washed coffees and the drying post-harvest treatment of Arabica or Robusta coffee brews. Kopi Luwak showed higher levels of caffeine and theophylline in comparison to the analyzed washed and unwashed Arabica coffees, as well as a different proportion of caffeoylquinic isomers. There was no difference between Kopi Luwak and other Arabica coffees in terms of the concentration of vitamin B3, amines, and phenolic acids. This was confirmed in PCA. The steaming and roasting of beans as well as the addition of black beans influence the concentration of 4-CQA and the nicotinic, ferulic, and quinic acids content.

Indolamines (e.g., serotonin and melatonin) are tryptophan-derived class of neurotransmitters and neuromodulators that play crucial roles in mood regulation, sleep-wake cycles, and gastrointestinal functions. These biogenic amines exert their effects by binding to specific receptors in the central nervous system, influencing neuronal activity and signalling cascades. Indolamines are vital in maintaining homeostasis, and imbalances in their levels have been implicated in various neurological and psychiatric disorders. Hence, in the present study, we have investigated the nonlinear properties of indolamines under a continuous wave (CW) and pulsed laser excitation using the closed-aperture (CA) Z-scan technique. The CA Z-scan is a cost-effective and sensitive analytical tool for investigating nonlinear properties. It is observed that indolamines show negative refractive and positive absorptive nonlinearity under in vitro physiological conditions. The origin of nonlinearity is ascribed to the thermo-optical effect governed by the saturated atomic absorption and molecular orientation mechanisms under CW and pulsed laser excitation, respectively. The strength of nonlinearity is found to vary linearly with the concentration of indolamines. Overall, serotonin possesses stronger nonlinearity than melatonin. The maximum nonlinearity (refractive index (n 2) & absorption coefficient (β)) for melatonin under CW and pulsed laser excitations are (-1.266 × 10−12 m2W−1 and -1.883 × 10−17 m2W−1) & (8.046 × 10−8 mW−1 and 1.516 × 10−13 mW−1), respectively. Meanwhile, the maximum n 2 and β under pulsed laser excitation for serotonin are obtained as -3.195 × 10−17 m2W−1 and 6.149 × 10−12 mW−1, respectively. The outcome of the results may be utilized in understanding processes mediated by indolamines and designing therapeutic interventions. [Display omitted] • Nonlinear properties of indolamines are studied under CW and pulsed laser excitations. • Indolamines exhibit negative refractive and positive absorptive nonlinearity. • Origin of nonlinearity is ascribed to the thermo-optical effect. • Strength of nonlinearity varies linearly with the concentration of indolamines. [ABSTRACT FROM AUTHOR]

• Type 1 diabetes increased the levels of Ca+ and cAMP-dependent protein kinases. • These kinases activates/regulates indolamines in various areas of rat brain. • These changes results in impairment of retinal, renal, neuronal and heart. • Insulin or respective pharmacological suppressors reversed these effects. • Dual inhibition of both Ca+ and cAMP-dependent pathways may be useful in diabetes. From early to later stages of Type I Diabetes Mellitus (TIDM), signalling molecules including brain indolamines and protein kinases are altered significantly, and that has been implicated in the Metabolic Disorders (MD) as well as impairment of retinal, renal, neuronal and cardiovascular systems. Considerable attention has been focused to the effects of diabetes on these signalling systems. However, the exact pathophysiological mechanisms of these signals are not completely understood in TIDM, but it is likely that hyperglycemia, acidosis, and insulin resistance play significant roles. Insulin maintains normal glycemic levels and it acts by binding to its receptor, so that it activates the receptor's tyrosine kinase activity, resulting in phosphorylation of several substrates. Those substrates provide binding/interaction sites for signalling molecules, including serine/threonine kinases and indolamines. For more than two decades, our research has been focused on the mechanisms of protein kinases, CaM Kinase and Serotonin transporter mediated alterations of indolamines in TIDM. In this review, we have also discussed how discrete areas of brain respond to insulin or some of the pharmacological agents that triggers or restores these signalling molecules, and it may be useful for the treatment of specific region wise changes/disorders of diabetic brain. [ABSTRACT FROM AUTHOR]

The present paper presents the evaluation of a mixed mode column (reversed phase and cation exchange) performance for the separation of 12 catecholamines, indolamines and their precursors and metabolites. The influence of different parameters, like organic modifier nature and percentage, salts nature and percentage, on the compounds separation was investigated. Good separation of the 12 selected compounds was obtained in the isocratic mode using a mobile phase composed of 90 % methanol and 10% ammonium acetate 20 mM, however the analysis time was excessively long (80 minutes). Thus an elution gradient was optimized and it reduced the analysis time to less than half (35 minutes).

For more than two decades, capillary electrophoresis (CE) was found to be a powerful tool in the separation of low molecular weight charged compounds, such as amino acids (AA). This article provides an overview on the current status of CE for analyzing AAs and their metabolites in biological and nonbiological samples. A survey of works published during the last 20 years is presented, underlining the main advantages brought by CE for the study of AAs and their amine metabolites, such as catecholamines, indolamines, histamine and other monoamines, as well as aminothiols. Sample preparation (including derivatization and concentration) and separation protocols were covered. Most AAs lack a strong UV chromophore, so the different detectors used in CE for their detection were described, including classical UV-Vis spectrophotometry, laser-induced fluorescence, mass spectrometry, electrochemistry, conductometry and chemiluminescence. The applications in life science and biotechnology were summarized. The advantages and limitations of CE analysis for AAs and future developments in this field were tentatively discussed. [ABSTRACT FROM PUBLISHER]

Abstract: Sex differences and gonadal hormone influences are well known for diverse aspects of forebrain amine and indolamine neurotransmitter systems, the cognitive and affective functions they govern and their malfunction in mental illness. This study explored whether hormone regulation/dysregulation of these systems could be related to gonadal steroid effects on catechol-O-methyltransferase and monoamine oxidase which are principal enzymatic controllers of forebrain dopamine, serotonin and norepinephrine levels. Driven by male over female differences in cortical enzyme activities, by male-specific associations between monoamine oxidase and catechol-O-methyltransferase gene polymorphisms and cognitive and dysfunction in disease and by male-specific consequences of gene knockouts in mice, the question of hormone sensitivity was addressed here using a male rat model where prefrontal dopamine levels and related behaviors are also known to be affected. Specifically, quantitative O-methylation and oxidative deamination assays were used to compare the activities of catechol-O-methyltransferase''s soluble and membrane-bound isoforms and of monoamine oxidase''s A and B isoforms in the pregenual medial prefrontal cortex and dorsal striatum of male rats that were sham operated, gonadectomized or gonadectomized and supplemented with testosterone propionate or with estradiol for 28 days. These studies revealed significant effects of hormone replacement but not gonadectomy on the soluble but not the membrane-bound isorfom of catechol-O-methyltransferase in both striatum and cortex. A significant, cortex-specific testosterone—but not estradiol—attenuated effect (increase) of gonadectomy on monoamine oxidase''s A but not B isoform was also observed. Although none of these actions suggest potential roles in the reguation/dysregulation of prefrontal dopamine, the suppressive effects of testosterone on cortical monoamine oxidase-A that were observed could have bearing on the increased incidence of cognitive deficits and symptoms of depression and anxiety that are repeatedly observed in males in conditions of hypogonadalism related to aging, other biological factors or in prostate cancer where androgen deprivation is used as a neoadjuvant treatment. [Copyright &y& Elsevier]

Abstract: Hyperglycemia and ketoacidosis are the two most serious factors in acute metabolic complications of both type 1 and type 2 diabetes. Dysfunction of the central nervous system is a well-documented complication of diabetes. We and others have previously reported that acute or chronic diabetes in animal''s results in altered brain neurotransmitter levels. In this study, we investigated the effects of acute (7 days) glucose-induced hyperglycemia and sodium acetoacetate (NaAcAc) or ammonium chloride (NH4Cl) induced acidosis on the level of indolamines (5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA)) as well as PKC-α expression/activity in discrete areas of rat brain. Glucose-induced (500mg/kg, bw) hyperglycemic (∼249mg%) rats showed significant (p <0.05) increase in 5-HT levels in mid brain (MB), pons medulla (PM) and cerebellum (CB), respectively. 5-HIAA level increased in hippocampus (HC) (p <0.05) as compared to control. The rats treated with sodium acetoacetate (NaAcAc) for 7 days (60mg/kg, bw) showed significant decrease (p <0.05) of 5-HT level in hypothalamus (HT). Whereas, the 5-HIAA level increased in MB (p <0.05). Similarly, the PKC-α expression as well as the enzyme activity showed significant increase in HC, MB, PM and CB under glucose-induced hyperglycemia and that changes correlated the changes of indolamines, suggesting that the hyperglycemia may be the major metabolic disorder in diabetic complications. [Copyright &y& Elsevier]

A specific capillary electrophoresis–time-of-flight mass spectrometry (CE–TOFMS) method for the determination of serotonin (5HT) and its precursors tryptophan (Trp) and 5-hydroxytryptophan (5HTP) in human platelet rich plasma is described. The analytes were removed from the plasma samples and preconcentrated by solid phase extraction (SPE) on mixed mode cation-exchange sorbents. The SPE recoveries were 71.6 ± 3.1 for 5HT, 91.0 ± 2.8 for Trp, and 95.3 ± 5.9% for 5HTP. Deuterated analogues of 5HT and Trp were used as internal standards for quantitation purposes. Submicromolar detection limits were obtained for standard mixtures of all compounds and their deuterated isotopes, except 5HTP, which had detection limits in the low micromolar range. The potential usefulness of this method in the clinical setting was demonstrated by analyzing plasma extracts from healthy volunteers as well as from pathological samples. While 5HTP was not present in any of the analyzed samples, the levels of 5HT and Trp in both normal and pathological plasma were determined. [Copyright &y& Elsevier]

Copper toxicity has been implicated in various neurodegenerative disorders such as Wilson's disease and Alzheimer's disease. Free copper in the brain is toxic and leads to neuronal and cellular damage, through free radical generation. Melatonin has been investigated as a possible copper ion chelator. Melatonin could prevent copper-induced neuronal and cellular damage through binding with copper and preventing copper-induced free radical generation. The effect of copper on pineal indolamine synthesis has not been studied extensively. In the present study, copper (2 mg/kg) and melatonin (12 mg/kg) were administered daily to Wistar rats for a 2-week and 6-week period. Pineal organ culture was utilized to monitor pineal indolamine synthesis. The pineals from the 2-week copper/melatonin-treated group showed a statistically significant decrease in 5-methoxytryptophol synthesis ( p < 0.01), compared to the pineals from the copper-treated group. Conversly, in the 6-week experiment, 5-methoxytryptophol synthesis was increased in both the copper- and copper/melatonin-treated groups. There was a statistically significant decrease in the N-acetyl serotonin level in the pineals from the 6-week copper-treated animals, as compared to the control- and copper/melatonin-treated group ( p < 0.01). These results imply that copper reduces N-acetyltransferase activity, which results in a decrease in N-acetyl serotonin synthesis. Melatonin when coadministered with copper appears to prevent the N-acetyltransferase inhibition by copper. Copper exerts contradictory effects on 5-methoxytryptophol synthesis. Further investigations need to be carried out to examine the effects of copper on the pineal enzymes. [ABSTRACT FROM AUTHOR]

Summary. Intra-striatal infusion of a high dose (100 μg/3 μl) of methamphetamine produced long-lasting depletions of striatal dopamine and serotonin in both male and female mice. Male mice exhibited a greater depletion of striatal dopamine and serotonin than female mice. A similar trend of sexual differences was observed when 4 cumulative doses of methamphetamine were administered systemically. Thus, the sexual differences in methamphetamine-induced neurotoxicity in the striatum are probably not due to their differences in peripheral metabolism of methamphetamine. Moreover, ovariectomized (OVX) mice supplemented with 3 daily doses of estradiol benzoate (EB) at high or physiological levels, 3 daily doses of progesterone (P), and 2 doses of EB followed by 1 dose of P all demonstrated higher striatal dopamine levels following methamphetamine treatment as compared to vehicle-supplemented controls. The OVX mice pretreated with 3 daily doses of P exhibited the highest striatal serotonin levels after methamphetamine administration of all groups. In conclusion, sexual differences observed in methamphetamine-induced striatal neurotoxicity may be modulated by ovarian hormones. [ABSTRACT FROM AUTHOR]