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Characterization of an important drug binding area on human serum albumin including the high-affinity binding sites of warfarin and azapropazone.

This paper reports a variety of experimental observations which strongly support the assumption that the warfarin binding site, or site I of … rugs to the azapropazone site with only minor effects on drugs bound to the warfarin site. The lone tryptophan residue of human serum albumin, previously shown to be part of the warfarin binding site, is obviously located in the not-overlapping part of the warfarin site, so that its modification affects only the binding of drugs to the warfarin and not to th …

Effects of dietary amino acids on brain amino acids and transmitter amines in rats with a portacaval shunt.

The etiologic relationship between disturbances in metabolism of amino acids and amines and hepatic coma was investigated by examining the effects of diets containing various mixtures of amino acids on brain amine metabolism in rats with a portacaval shunt, using a method for simultaneous analysis of amino acids and amines. Rats with a portacaval shunt were fed on four different amino acid compositions with increased amounts of various amino acids suspected to be etiologically related to hepatic coma, such as methionine, phenylalanine, tyrosine, and tryptophan. The animals were killed 4 weeks …

Interactions of corticosterone, 5alpha-dihydrocorticosterone and dexamethasone with proteins in rat-liver cytosol.

The intracellular binding of [3H]corticosterone and [3H]dexamethasone and their metabolites to macromolecules in rat liver cytosol was studi … ding sites on the receptor. An assay of the inductive effect on liver tyrosine aminotransferase and tryptophan oxygenase indicated that 5alpha-dihydrocorticosterone was practically devoid of glucocorticoid activity. It is concluded that 5alpha-dihydrocorticosterone probably does not act as the mediator of corticosterone action in rat liver.

Investigations on the venom of the South Indian scorpion Heterometrus scaber.

The enzymes from the venom of Heterometrus scaber, the indole compounds present and the toxic protein of the venom have been studied. The venom contains acid phosphatase, ribonuclease, 5'-nucleotidase, hyaluronidase, acetylcholine esterase and phospholipase. A. The indole compounds present in the venom have been identified as 5-hydroxytryptophan, tryptophan, serotonin and tryptamine, along with two unidentified indole compounds. The venom produces hyperglycaemia in sublethal doses and this has been found to be due to increased adrenaline secretion. The toxic protein of the venom has been obtai…

Generation of Infectious Prions Amenable to Site-specific Click Chemistry.

Prion diseases are a group of fatal neurodegenerative diseases that proceed through the templated conversion of the normal PrP C protein to a self-propagating and infectious form, termed PrP Sc . This conversion process is central to disease progression. However, due to difficulties in producing functional PrP Sc molecules that can be selectively modified with chemical probes, many aspects of PrP Sc biology cannot be directly studied. To overcome this limitation, we substituted p-azido-L-phenylalanine (AzF), a small click chemistry-reactive amino acid, for tryptophan residue 99 of PrP C . W99A…

Identification and In Silico Selection of Novel Antioxidant Peptides from Asian Swamp Eel Bone: Quantum Chemical Calculations, Molecular Docking, and Zebrafish Model Validation.

Fourteen novel antioxidant peptides were screened from the enzymatic hydrolysates of Asian swamp eel bone (ASEB) through an in silico analysis. Their ABTS and ORAC radical scavenging capacities were 1.70-4.29-fold and 2.79-5.90-fold higher than those of Trolox, respectively. Additionally, two novel peptide sequences (NVGW and WALN) were identified. Quantum chemical calculations combined with active--site methylation experiments demonstrated that hydrogen atoms on tryptophan's indole nitrogen, tyrosine's phenolic hydroxyl, and arginine's guanidinium group play crucial roles in enhancing ABTS an…

Molecular mechanisms for subtype selectivity of kinin receptors' antagonists.

The kinin receptors B1R and B2R act as key regulators within the kallikrein-kinin system, mediating vasodilation, inflammation, and pain. An … R and B2R, wherein the antagonist binding restricts the conformational changes of the toggle switch tryptophan residue. Collectively, these insights lay the foundation for the structure-based design of selective antagonists targeting B1R and B2R.

Current applications and development of dual-target inhibitors of Ido1/TDO: From tumor immunology to neuropsychiatric disorders.

Indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan 2,3-dioxygenase (TDO) are rate-limiting enzymes of the kynurenine pathway and are closely associated with tumor immune evasion and neuropsychiatric disorders. The failure of single-target IDO1 inhibition, exemplified by the phase III setback of epacadostat, has highlighted the limitations imposed by compensatory TDO activity and the heterogeneity of the tumor microenvironment. This review focuses on three generations of IDO1 inhibitors, selective TDO inhibitors, and emerging dual-target strategies, and provides a comprehensive overview of IDO…

Mechanistic Insights Into the Photosensitizing Properties of the Topical Retinoid Tazarotene.

Since the FDA approval of tretinoin in 1971, retinoids have been key in treating acne and different skin pathologies. Tazarotene (TZE), a th … es, which interact with oxygen to produce reactive singlet oxygen. Additionally, TZA interacts with tryptophan (Trp), leading to the formation of a photoproduct with a mass corresponding to a Trp/TZA cyclobutene adduct. These results correlate with reduced cell viability in fibroblasts exposed to light after treatment with TZE or TZA, indicating potential ph …

Polylactic acid microplastics as metabolic disruptors: Linking gut dysbiosis to systemic toxicity by disrupting microbiota-host co-metabolism.

The increasing application of polylactic acid (PLA) in consumer products leads to the widespread environmental distribution of its micro- an … ted gut microbiota-host co-metabolism - particularly involving aromatic amino acid pathways such as tryptophan metabolism - as a potential mechanism linking PLA-MNPs exposure to intestinal inflammation and injury, while acknowledging the current lack of direct experimental evidence for PLA-MNPs-specific effects on these pathways. By integrating literature on …

A CLN8 biallelic missense variant causes epilepsy with severe treatment-resistant psychosis.

Epilepsy and psychosis are dysfunctions of the nervous system that may occasionally co-occur. The current study was designed to investigate … h is conserved in diverse vertebrate orthologues. In-silico analysis indicated that substitution of tryptophan with cysteine resulted in the loss of an intramolecular interaction, which may affect protein folding. This study emphasizes that CLN8-related phenotype can include severe treatment-resistant psychosis and also provides a genotypic extension.

Pathobiont-triggered induction of goblet cell response drives regional susceptibility to inflammatory bowel disease.

The gastrointestinal tract varies in structure and function by region, yet the drivers of region-specific inflammatory disease remain elusiv … s, pathobiont-triggered proximal colonic inflammation is driven by goblet cell responses, including tryptophan metabolism via indoleamine 2,3-dioxygenase 1 (IDO1). Our findings translate to human disease, where we demonstrate upregulation of epithelia-derived IDO1 in actively inflamed ascending colon specimens, but not actively inflamed terminal ileum specim …

Potential roles of the melatonin system in the promotion of ovarian estradiol secretion in the sea cucumber, Apostichopus japonicus.

Melatonin (MT), synthesized from tryptophan, modulates reproduction through its interaction with melatonin receptors (MTNRs). While its functions in vertebrates are well established, the MT system remains poorly understood in echinoderms. To elucidate MT synthesis regulation, we examined AjAsmt, a pivotal enzyme in MT biosynthesis, to determine its tissue-specific distribution in Apostichopus japonicus. AjAsmt was predominantly expressed in the nerve ring, polian vesicle, intestine, and muscle, with significantly reduced intestinal expression post-spawning, suggesting a role in ovarian develop…

Role of Glial Trace Amine Associated Receptor 1 (TAAR1) and Microbiota in Schizophrenia.

Trace amine-associated receptors (TAARs) are a class of G protein-coupled receptors that respond to metabolic derivatives of the amino acids such as phenylalanine, tyrosine, and tryptophan. Trace amines derive their name from the fact that their concentration in the periphery as well as in the central nervous system (CNS) is in trace amounts compared to the parent compound or other monoamine neurotransmitters such as dopamine, norepinephrine, or serotonin. Genetic, pharmacological and neurobiological studies have linked TAAR1, the most studied receptor of the TAARs to the pathophysiology of sc…

Immunometabolism: The role of gut-derived microbial metabolites in optimising immune response during checkpoint inhibitor therapy.

Checkpoint inhibitor therapy is the most common type of immunotherapy used in the clinical setting, however, there are significant obstacles … immunoregulatory molecules shaping T-cell activation, effector and memory function. We then discuss tryptophan catabolism as a key predictor of primary checkpoint inhibitor failure. Lastly, we focus on immunometabolism as an important future target in immunotherapy. ONE SENTENCE SUMMARY: This review focusses on microbiome-derived metabolites and their role i …

The Aryl Hydrocarbon Receptor (AHR): Peacekeeper of the Skin.

In the last decade, the aryl hydrocarbon receptor (AHR) has emerged as a critical peacekeeper for the maintenance of healthy skin. The evolutionary conservation of AHR implied physiological functions for this receptor, beyond the detoxification of man-made compounds, a notion further supported by the existence of physiological AHR ligands, notably derivates of tryptophan by the host and host microbiome. The UV light-derived ligand, 6-formylindolo[3,2-b]carbazole (FICZ), anticipated a role for AHR in skin, a UV light-exposed organ, where physiological AHR activation promotes a healthy skin barr…

Gut microbiota metabolites in the immunoregulation of enteritis: research progress.

The interaction between gut microbiota metabolites and the host immune system plays a crucial role in maintaining intestinal homeostasis and in the development of inflammatory bowel disease and other enteric conditions. This article presents a systematic review of the sources and functions of short-chain fatty acids, tryptophan metabolites, bile acids, and other microbial metabolites, focusing on how these metabolites regulate the function of immune cells, such as T cells, B cells, neutrophils, macrophages, and dendritic cells, as well as key inflammatory signaling pathways, including the NF-κ…

Невозмутимый множественный склероз: скрытое взаимодействие между кишечной микробиотой и липидным метаболизмом.

Регулирование структуры кишечного микробиота тесно связано с риском возникновения и развития множественных склерозов. Сложное взаимодействие между кишечной микробиотой и липидным метаболизмом, по всей вероятности, является одним из ключевых путей, содействующих этой взаимосвязи: кишечная микробиота прямо или косвенно изменяет липидный метаболизм (включая холестерол, фосфолипиды, фосфолипиды и жирные кислоты) путем контроля за производством конкретных метаболитов (таких, как короткоцепные жирные кислоты, метаболиты триптофана, желчные кислоты, триметиламин-N-оксид и липополиачариды), тем самым

Совпадение в аннотации оригинала
Dysregulation of the structure of the gut microbiota is closely linked to the risk of onset and progression of multiple sclerosis. The intri … atty acids) by controlling the production of specific metabolites (such as short-chain fatty acids, tryptophan metabolites, bile acids, trimethylamine-N-oxide, and lipopolysaccharides), thereby impacting core pathological processes in multiple sclerosis. Therefore, elucidating the specific roles and mechanisms of the gut microbiota in modulating lipid metabo …

Metabolomic profiling of cancer-related fatigue involved in cachexia and chemotherapy.

Patients with advanced cancer are frequently burdened with a severe sensation of fatigue called cancer-related fatigue (CRF). CRF is induced … ia or chemotherapy-induced fatigue, were compared. Significantly lower concentrations of valine and tryptophan were observed in fatigued patients than in non-fatigued patients. In addition, significantly higher concentrations of polyamine pathway metabolites were observed in patients with fatigue and cachexia than in those without cachexia. Patients with exa …

The Protective Effect of Walnut Oligopeptides against Indomethacin-Induced Gastric Ulcer in Rats.

The aim of this study was to investigate the potential protective effects of walnut oligopeptides (WOPs) on indomethacin-induced gastric ulc … mechanism may be related to the involvement of the arachidonic acid metabolism and upregulation of tryptophan, phenylalanine, tyrosine, and alpha-Linolenic acid metabolism synthesis in vivo.