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tryptophan hydroxylase

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https://www.readbyqxmd.com/read/29653078/characterization-of-cyri-the-hydroxylase-involved-in-the-last-step-of-cylindrospermopsin-biosynthesis-binding-studies-site-directed-mutagenesis-and-stereoselectivity
#1
Rabia Mazmouz, Insaf Essadik, Djemel Hamdane, Annick Méjean, Olivier Ploux
Cylindrospermopsin, a cytotoxin from cyanobacteria, is biosynthesized by a complex pathway, which involves CyrI, an iron and 2-oxoglutarate dependent hydroxylase that transforms 7-deoxy-cylindrospermopsin into cylindrospermopsin and its epimer, 7-epi-cylindrospermopsin, in the last step. The activity of CyrI from Oscillatoria sp. PCC 7926 depends on Fe(II) (Km  = 2.1 μM), and 2-oxoglutarate (Km  = 3.2 μM), and is strongly inhibited by 7-deoxy-cylindrospermopsin at concentration higher than 1 μM...
April 10, 2018: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/29628275/peripheral-serotonin-synthesis-as-a-new-drug-target
#2
REVIEW
Susann Matthes, Michael Bader
The first step in serotonin (5-HT) biosynthesis is catalyzed by tryptophan hydroxylase (TPH). There are two independent sources of the monoamine that have distinct functions: first, the TPH1-expressing enterochromaffin cells (ECs) of the gut; second, TPH2-expressing serotonergic neurons. TPH1-deficient mice revealed that peripheral 5-HT plays important roles in platelet function and in inflammatory and fibrotic diseases of gut, pancreas, lung, and liver. Therefore, TPH inhibitors were developed which cannot pass the blood-brain barrier to specifically block peripheral 5-HT synthesis...
April 5, 2018: Trends in Pharmacological Sciences
https://www.readbyqxmd.com/read/29625215/h3k9-acetylation-of-tph2-involved-in-depression-like-behavior-in-male-but-not-female-juvenile-offspring-rat-induced-by-prenatal-stress
#3
Shaokang Dang, Yong Lu, Qian Su, Tianwei Lin, Xiaoxiao Zhang, Huiping Zhang, Junli Zhang, Lin Zhang, Zhongliang Zhu, Hui Li
Increasing evidence has shown that prenatal stress (PS) could cause depression-like behavior in the offspring, which is sex-specific. However, the underlying mechanisms remain to be elucidated. This study is to investigate the involvement of tryptophan hydroxylase 2 (Tph2) H3K9 acetylation (H3K9ac) modification on PS-induced depression-like behavior in juvenile offspring rats (JOR). PS models were established, with or without trichostatin A (TSA) treatment. Animal behavior was assessed by the sucrose preference test (SPT) and forced swimming test (FST)...
April 3, 2018: Neuroscience
https://www.readbyqxmd.com/read/29623884/tryptophan-metabolism-utility-of-plasmatic-assay-in-phenylketonuria-a-study-in-6-adult-patients
#4
Lysiane Boulet, Gérard Besson, Patrice Faure, Véronique Ducros, Christelle Corne
Phenylketonuria (PKU, OMIM 261600) is an autosomal recessive inborn error of metabolism caused by a deficiency of the hepatic enzyme phenylalanine hydroxylase (PAH; EC 1.14.16.1). If untreated, the disease leads to an important intellectual disability (IQ <50). Although many facts are common between phenylalanine (Phe) and tryptophan (Trp) metabolism, little is known about Trp metabolism modification in PKU. Our aim was to evaluate the modifications of Trp metabolism in a phenylketonuric population. A monocentric study was conducted between October 2016 and March 2017...
April 1, 2018: Annales de Biologie Clinique
https://www.readbyqxmd.com/read/29621775/association-of-polymorphisms-of-serotonin-transporter-5httlpr-and-5-ht2c-receptor-genes-with-criminal-behavior-in-russian-criminal-offenders
#5
Valentina A Toshchakova, Yalda Bakhtiari, Alexander V Kulikov, Sergey I Gusev, Marina V Trofimova, Olga Yu Fedorenko, Ekaterina V Mikhalitskaya, Nina K Popova, Nikolay A Bokhan, Johannes E Hovens, Anton J M Loonen, Bob Wilffert, Svetlana A Ivanova
BACKGROUND: Human aggression is a heterogeneous behavior with biological, psychological, and social backgrounds. As the biological mechanisms that regulate aggression are components of both reward-seeking and adversity-fleeing behavior, these phenomena are difficult to disentangle into separate neurochemical processes. Nevertheless, evidence exists linking some forms of aggression to aberrant serotonergic neurotransmission. We determined possible associations between 6 serotonergic neurotransmission-related gene variants and severe criminal offenses...
April 5, 2018: Neuropsychobiology
https://www.readbyqxmd.com/read/29617866/serotonin-induces-parathyroid-hormone-related-protein-in-goat-mammary-gland
#6
W J Zang, H Li, Z F Zhang, R QuZhen, Y Z CuoMu, D K Zhang, J Luo, J J Loor, H L Zheng
During lactation, large amounts of calcium are exported from the mammary gland into milk to ensure skeletal growth of the offspring. Recent studies revealed that serotonin (5-HT) is essential to stimulate skeletal calcium resorption for milk synthesis. Our objective was to explore the correlation between circulating 5-HT and serum calcium and parathyroid hormone-related protein (PTHrP) concentrations around parturition in dairy goats. We also investigated the effect of 5-HT on PTHrP expression in cultured primary goat mammary epithelial cells (GMEC)...
April 3, 2018: Journal of Animal Science
https://www.readbyqxmd.com/read/29608654/the-ventrolateral-medulla-and-medullary-raphe-in-sudden-unexpected-death-in-epilepsy
#7
Smriti Patodia, Alyma Somani, Megan O'Hare, Ranjana Venkateswaran, Joan Liu, Zuzanna Michalak, Matthew Ellis, Ingrid E Scheffer, Beate Diehl, Sanjay M Sisodiya, Maria Thom
Sudden unexpected death in epilepsy (SUDEP) is a leading cause of premature death in patients with epilepsy. One hypothesis proposes that sudden death is mediated by post-ictal central respiratory depression, which could relate to underlying pathology in key respiratory nuclei and/or their neuromodulators. Our aim was to investigate neuronal populations in the ventrolateral medulla (which includes the putative human pre-Bötzinger complex) and the medullary raphe. Forty brainstems were studied comprising four groups: 14 SUDEP, six epilepsy controls, seven Dravet syndrome cases and 13 non-epilepsy controls...
March 28, 2018: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/29589922/mutagenesis-of-an-active-site-loop-in-tryptophan-hydroxylase-dra-matically-slows-the-formation-of-an-early-intermediate-in-catalysis
#8
Bishnu P Subedi, Paul F Fitzpatrick
Solution studies of the aromatic amino acid hydroxylases are consistent with the FeIVO intermediate not forming until both the amino acid and tetrahydropterin substrates have bound. Structural studies have shown that the positions of active-site loops differs significantly between the free enzyme and the enzyme-amino acid-tetrahydropterin complex. In tryptophan hydroxylase (TrpH) these mobile loops contain residues 124-134 and 365-371, with a key interaction involving Ile366. The I366N mutation in TrpH results in decreases of 1-2 orders of magnitude in the kcat and kcat/Km values...
March 28, 2018: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/29569002/mast-cells-and-serotonin-synthesis-modulate-chagas-disease-in-the-colon-clinical-and-experimental-evidence
#9
Vinicius Kannen, Juliana Y Sakita, Zumira A Carneiro, Michael Bader, Natalia Alenina, Regina R Teixeira, Enio C de Oliveira, Mariângela O Brunaldi, Bianca Gasparotto, Daniela C Sartori, Cleverson R Fernandes, João S Silva, Marcus V Andrade, Wilson A Silva, Sergio A Uyemura, Sérgio B Garcia
BACKGROUND: Trypanosoma cruzi (T. cruzi) infects millions of Latin Americans each year and can induce chagasic megacolon. Little is known about how serotonin (5-HT) modulates this condition. Aim We investigated whether 5-HT synthesis alters T. cruzi infection in the colon. MATERIALS AND METHODS: Forty-eight paraffin-embedded samples from normal colon and chagasic megacolon were histopathologically analyzed (173/2009). Tryptophan hydroxylase 1 (Tph1) knockout (KO) mice and c-KitW-sh mice underwent T...
March 22, 2018: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/29568327/synthetic-pathways-and-processes-for-effective-production-of-5-hydroxytryptophan-and-serotonin-from-glucose-in-escherichia-coli
#10
José-Aníbal Mora-Villalobos, An-Ping Zeng
Background: Tryptophan derivatives such as 5-hydroxytryptophan (5HTP) and serotonin are valuable molecules with pharmaceutical interest. 5HTP is presently mainly obtained by extraction from the plant Griffonia simplicifolia and serotonin is produced by chemical synthesis. A simple biotechnological method for the production of these compounds is desired. Results: In a first attempt to synthesize serotonin from glucose, we used a single engineered Escherichia coli strain and observed a low production of maximal 0...
2018: Journal of Biological Engineering
https://www.readbyqxmd.com/read/29568107/augmented-capacity-for-peripheral-serotonin-release-in-human-obesity
#11
Richard L Young, Amanda L Lumsden, Alyce M Martin, Gudrun Schober, Nektaria Pezos, Sony S Thazhath, Nicole J Isaacs, Nada Cvijanovic, Emily W L Sun, Tongzhi Wu, Christopher K Rayner, Nam Q Nguyen, Dayan de Fontgalland, Philippa Rabbitt, Paul Hollington, Luigi Sposato, Steven L Due, David A Wattchow, Alice P Liou, V Margaret Jackson, Damien J Keating
BACKGROUND/OBJECTIVES: Evidence from animal studies highlights an important role for serotonin (5-HT), derived from gut enterochromaffin (EC) cells, in regulating hepatic glucose production, lipolysis and thermogenesis, and promoting obesity and dysglycemia. Evidence in humans is limited, although elevated plasma 5-HT concentrations are linked to obesity. SUBJECTS/METHODS: We assessed (i) plasma 5-HT concentrations before and during intraduodenal glucose infusion (4 kcal/min for 30 min) in non-diabetic obese (BMI 44 ± 4 kg/m2 , N = 14) and control (BMI 24 ± 1 kg/m2 , N = 10) subjects, (ii) functional activation of duodenal EC cells (immunodetection of phospho-extracellular related-kinase, pERK) in response to glucose, and in separate subjects, (iii) expression of tryptophan hydroxylase-1 (TPH1) in duodenum and colon (N = 39), and (iv) 5-HT content in primary EC cells from these regions (N = 85)...
March 1, 2018: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/29567680/chronic-intake-of-the-selective-serotonin-reuptake-inhibitor-fluoxetine-enhances-atherosclerosis
#12
Martina Rami, Raquel Guillamat-Prats, Petteri Rinne, Melanie Salvermoser, Larisa Ring, Mariaelvy Bianchini, Xavier Blanchet, Remco T A Megens, Yvonne Döring, Barbara Walzog, Oliver Soehnlein, Christian Weber, Alexander Faussner, Sabine Steffens
OBJECTIVE: Cardiovascular diseases and depression are the leading causes of disability in Western countries. Clinical data on potential cardiovascular effects of serotonin reuptake inhibitors (SSRIs), the most commonly used antidepressant drugs, are controversial. In addition to blocking serotonin reuptake transporter in the brain, SSRIs deplete the major peripheral serotonin (5-hydroxytryptamine [5-HT]) storage by inhibiting serotonin reuptake transporter-mediated uptake in platelets...
March 22, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29548669/catalytic-modulation-of-human-cytochromes-p450-17a1-and-p450-11b2-by-phospholipid
#13
Hwei-Ming Peng, Chase Barlow, Richard J Auchus
Unlike most of the drug-metabolizing cytochrome P450s, microsomal P450 17A1 and mitochondrial P450 11B2 catalyze sequential multi-step reactions in steroid biosynthesis. The membrane phospholipid composition might be one parameter that modulates the efficiency and processivity of specific pathways. Here we systematically examined the effects of physiologically relevant phospholipids on the catalysis of purified P450 17A1, P450 11B2, and P450 11B1 in reconstituted assay systems. Both dioleoylphosphatidylcholine (DOPC, 18:1) and dilauroylphosphatidylcholine (DLPC, 12:0) were found to be very efficient in reconstituting 17-hydroxylase and 17,20-lyase reactions of P450 17A1...
March 13, 2018: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/29542343/interplay-between-the-key-proteins-of-serotonin-system-in-ssri-antidepressants-efficacy
#14
Alexander V Kulikov, Raul R Gainetdinov, Evgeni Ponimaskin, Allan V Kalueff, Vladimir S Naumenko, Nina K Popova
Selective serotonin reuptake inhibitors (SSRIs) are the most effective and most used antidepressant drugs. Acting by inhibiting serotonin (5-HT) transporter, SSRIs display a typical 3-4-week delay in their therapeutic effects, with nearly 40% of depressed patients remaining treatment-resistant. Recent evidence suggests complex interplay between 5-HT receptors and key proteins of 5-HT metabolism in molecular mechanisms of such delay and resistance to SSRIs. Area covered: This paper concentrates on the interplay between 5-HT receptors in the delay of therapeutic effect of SSRIs, and the interaction between tryptophan hydroxylase 2 and 5-HT transporter in the SSRI resistance...
March 15, 2018: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/29520738/tetrahydrobiopterin-treatment-reduces-brain-l-phe-but-only-partially-improves-serotonin-in-hyperphenylalaninemic-enu1-2-mice
#15
Tanja Scherer, Gabriella Allegri, Christineh N Sarkissian, Ming Ying, Hiu Man Grisch-Chan, Anahita Rassi, Shelley R Winn, Cary O Harding, Aurora Martinez, Beat Thöny
Hyperphenylalaninemia (HPA) caused by hepatic phenylalanine hydroxylase (PAH) deficiency has severe consequences on brain monoamine neurotransmitter metabolism. We have studied monoamine neurotransmitter status and the effect of tetrahydrobiopterin (BH4 ) treatment in Pahenu1/enu2 (ENU1/2) mice, a model of partial PAH deficiency. These mice exhibit elevated blood L-phenylalanine (L-Phe) concentrations similar to that of mild hyperphenylalaninemia (HPA), but brain levels of L-Phe are still ~5-fold elevated compared to wild-type...
March 8, 2018: Journal of Inherited Metabolic Disease
https://www.readbyqxmd.com/read/29516654/effects-of-neonatal-hyperoxia-on-the-critical-period-of-postnatal-development-of-neurochemical-expressions-in-brain-stem-respiratory-related-nuclei-in-the-rat
#16
Lianwei Mu, Dong Dong Xia, Teresa Michalkiewicz, Matthew Hodges, Gary Mouradian, Girija G Konduri, Margaret T T Wong-Riley
We have identified a critical period of respiratory development in rats at postnatal days P12-13, when inhibitory influence dominates and when the response to hypoxia is at its weakest. This critical period has significant implications for Sudden Infant Death Syndrome (SIDS), the cause of which remains elusive. One of the known risk factors for SIDS is prematurity. A common intervention used in premature infants is hyperoxic therapy, which, if prolonged, can alter the ventilatory response to hypoxia and induce sustained inhibition of lung alveolar growth and pulmonary remodeling...
March 2018: Physiological Reports
https://www.readbyqxmd.com/read/29515602/development-of-biofortified-maize-hybrids-through-marker-assisted-stacking-of-%C3%AE-carotene-hydroxylase-lycopene-%C3%AE%C2%B5-cyclase-and-opaque2-genes
#17
Rajkumar U Zunjare, Firoz Hossain, Vignesh Muthusamy, Aanchal Baveja, Hema S Chauhan, Jayant S Bhat, Nepolean Thirunavukkarasu, Supradip Saha, Hari S Gupta
Traditional yellow maize though contains high kernel carotenoids, the concentration of provitamin A (proA) is quite low (<2 μg/g), compared to recommended level (15 μg/g). It also possesses poor endosperm protein quality due to low concentration of lysine and tryptophan. Natural variant of crtRB1 (β -carotene hydroxylase ) and lcyE ( lycopene- ε -cyclase ) cause significant enhancement of proA concentration, while recessive allele, opaque2 ( o2 ) enhances the level of these amino acids. Development of biofortified maize enriched in proA, lysine and tryptophan thus holds significance in alleviation of micronutrient malnutrition...
2018: Frontiers in Plant Science
https://www.readbyqxmd.com/read/29503551/developments-in-the-treatment-of-carcinoid-syndrome-impact-of-telotristat
#18
REVIEW
David L Chan, Simron Singh
Carcinoid syndrome occurs in 20% of patients with neuroendocrine tumors, and serotonin is usually the main causative hormonal peptide. Carcinoid syndrome, and particularly diarrhea, can significantly impact patients' quality of life. Somatostatin analogs (SSAs) are the mainstay of treatment, but are unable to ameliorate symptoms in all patients due to dose-limiting side effects and tachyphylaxis. Telotristat is a novel oral inhibitor of tryptophan hydroxylase, which is the rate-limiting enzyme in serotonin synthesis...
2018: Therapeutics and Clinical Risk Management
https://www.readbyqxmd.com/read/29486157/abnormalities-of-the-serotonergic-system-in-diacylglycerol-kinase-%C3%AE-deficient-mouse-brain
#19
Qiang Lu, Suguru Komenoi, Takako Usuki, Daisuke Takahashi, Fumio Sakane
We previously reported that brain-specific diacylglycerol kinase (DGK) δ-knockout (KO) mice showed obsessive-compulsive disorder (OCD)-like behaviors, which were alleviated by a serotonin (5-HT) transporter (SERT) inhibitor. However, the molecular mechanisms causing the OCD-like abnormal behaviors remain unclear. In the present study, we found that DGKδ deficiency increased SERT protein levels in the mouse cerebral cortex. Moreover, DGKδ interacted and co-localized with SERT. Furthermore, DGKδ-KO decreased tryptophan hydroxylase-2 expression and increased monoamine oxidase-A expression...
February 24, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29484303/liraglutide-a-glp-1-receptor-agonist-which-decreases-hypothalamic-5-ht2a-receptor-expression-reduces-appetite-and-body-weight-independently-of-serotonin-synthesis-in-mice
#20
Katsunori Nonogaki, Takao Kaji
A recent report suggested that brain-derived serotonin (5-HT) is critical for maintaining weight loss induced by glucagon-like peptide-1 (GLP-1) receptor activation in rats and that 5-HT2A receptors mediate the feeding suppression and weight loss induced by GLP-1 receptor activation. Here, we show that changes in daily food intake and body weight induced by intraperitoneal administration of liraglutide, a GLP-1 receptor agonist, over 4 days did not differ between mice treated with the tryptophan hydroxylase (Tph) inhibitor p-chlorophenylalanine (PCPA) for 3 days and mice without PCPA treatment...
2018: Journal of Diabetes Research
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