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The Chemistry of the Brain
Published in Gail S. Anderson, Biological Influences on Criminal Behavior, 2019
TPH1 is one of the genes involved in the conversion of dietary tryptophan to serotonin. This meta-analysis involved 25 studies on polymorphisms of this gene. Most studies showed a link between some variants of this gene and violent suicide attempts, although different alleles were involved, and some studies showed no links. The strongest links were among Caucasians.10 There was no consistent relationship between the other candidate genes and suicidal behavior unless very specific types of suicide were considered separately, such as level of violence, anger, and impulsivity, in which cases positive links were seen between TPH1, HTR2A, and MAO. Gene × environment interactions were also seen in some polymorphisms of 5-HTTLPR, HTR2A, and MAO with adverse life experiences.10
The biological bases of personality
Published in Philip N. Murphy, The Routledge International Handbook of Psychobiology, 2018
Attempts to identify the genetic basis of borderline personality disorder have been less successful. These studies are often focused on the serotonin system. For example, Maurex et al. (2009) linked impaired decision-making in those with borderline personality disorder to the Tryptophan hydroxylase-1 (TPH1) gene (responsible for the synthesis of peripheral serotonin), suggesting that the impaired decision-making in those with borderline personality disorder is associated with serotonin dysfunction. However, a recent meta-analysis found no significant associations between borderline personality disorder and the TPH1 gene or serotonin transporter (5-HHT) gene (Amad, Ramoz, Thomas, Jardri, & Gorwood, 2014), demonstrating the inconsistency in this area. It is, of course, important to consider the influence of both biological and environmental factors. For example, those with borderline personality disorder often report physical or sexual abuse or neglect during childhood (Zanarini et al., 2002). Most studies investigating the causes of disorders such as borderline personality disorder (or in fact personality traits per se) do not consider both biological and environmental causes. Significant interactions between genotype and environmental factors such as abuse history appear likely, and future research should investigate these interactions further (Wilson et al., 2012).
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).
Gut microbiota-motility interregulation: insights from in vivo, ex vivo and in silico studies
Published in Gut Microbes, 2022
Barbora Waclawiková, Agnese Codutti, Karen Alim, Sahar El Aidy
It is well accepted that the greatest quantity of serotonin (5-HT) in the human body is synthesized within a subtype of the enteroendocrine cells, enterochromaffin cells, in the intestinal mucosa, via the enzyme tryptophan hydroxylase 1 (TPH1).78 Enterochromaffin cells act as sensory transducers to release 5-HT in response to various mechanical and chemical stimuli.79 In 2017, enterochromaffin cells were recognized as specialized stimulus detectors that constitute a direct line of communication between the mouse gut epithelium and enteric nervous system.80 A year later, it was shown that, throughout the mouse gut, enterochromaffin cells release 5-HT in response to their sensing of nutrients and microbial metabolites, indirectly through the release of GLP-1 by neighboring cells.81
Host–microbiome interactions: the aryl hydrocarbon receptor as a critical node in tryptophan metabolites to brain signaling
Published in Gut Microbes, 2020
Ning Ma, Ting He, Lee J. Johnston, Xi Ma
Serotonin is a pivotal neurotransmitter that is present in the gut (~95%) and CNS (~5%).57 It is produced in enterochromaffin (EC) cells via Trp hydroxylase 1 (TpH1).58 Moreover, it has also been reported that indigenous spore-forming bacteria present in mouse and human microbiota could accelerate serotonin generation in colonic EC cells.58,59 These cells carry TpH1, an enzyme that is responsible for the degradation of Trp into 5-hydroxytryptophan, a short-lived metabolite that is further decarboxylated to serotonin by aromatic amino acid decarboxylase (AAAD). Moreover, certain microbiota can directly utilize Trp to synthesize serotonin in vitro.60 The serotonin can be further degraded along two metabolic pathways by different enzymes, whereby monoamine oxidase (MAO) is responsible for the metabolic conversion of most serotonin to 5-hydroxyindoleacetic acid (5-HIAA). In another serotonin catabolism route, melatonin can be produced through the decomposition of serotonin in the pineal gland (Figure 3).
Tryptophan hydroxylase 2 as a therapeutic target for psychiatric disorders: focus on animal models
Published in Expert Opinion on Therapeutic Targets, 2019
Elizabeth A. Kulikova, Alexander V. Kulikov
TPH1 is expressed in periphery and the pineal gland [7,8]. Information about the expression of TPH1 in the brain is rather contradictory. Several authors found Tph1 mRNA in this organ in human; however, its level is approximately four to six times less abundant than that of Tph2 mRNA [34,35]. In our study we found only trace amounts of Tph1 mRNA in the mouse brain; this result is in good accordance with the data of some other authors [see 30]. Moreover, Tph1 gene knockout reduces the 5-HT level in the mouse brain only by 3% [7,25]. Anyway, the role of TPH1 in the brain 5-HT synthesis and, therefore, in the regulation of the brain function and behavior seems to be less important in comparison with that of TPH2.