Journal ArticleDOI
Blood–Brain Barrier Transport of Kynurenines: Implications for Brain Synthesis and Metabolism
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TLDR
The results demonstrate the saturable transfer of L‐KYN across the blood–brain barrier and suggest that circulating L‐ KYN, 3‐HKYN, and ANA may each contribute significantly to respective cerebral pools under normal conditions.Abstract:
To evaluate the potential contribution of circulating kynurenines to brain kynurenine pools, the rates of cerebral uptake and mechanisms of blood-brain barrier transport were determined for several kynurenine metabolites of tryptophan, including L-kynurenine (L-KYN), 3-hydroxykynurenine (3-HKYN), 3-hydroxyanthranilic acid (3-HANA), anthranilic acid (ANA), kynurenic acid (KYNA), and quinolinic acid (QUIN), in pentobarbital-anesthetized rats using an in situ brain perfusion technique. L-KYN was found to be taken up into brain at a significant rate [permeability-surface area product (PA) = 2-3 x 10(-3) ml/s/g] by the large neutral amino acid carrier (L-system) of the blood-brain barrier. Best-fit estimates of the Vmax and Km of saturable L-KYN transfer equalled 4.5 x 10(-4) mumol/s/g and 0.16 mumol/ml, respectively. The same carrier may also mediate the brain uptake of 3-HKYN as D,L-3-HKYN competitively inhibited the brain transfer of the large neutral amino acid L-leucine. For the other metabolites, uptake appeared mediated by passive diffusion. This occurred at a significant rate for ANA (PA, 0.7-1.6 x 10(-3) ml/s/g), and at far lower rates (PA, 2-7 x 10(-5) ml/s/g) for 3-HANA, KYNA, and QUIN. Transfer for KYNA, 3-HANA, and ANA also appeared to be limited by plasma protein binding. The results demonstrate the saturable transfer of L-KYN across the blood-brain barrier and suggest that circulating L-KYN, 3-HKYN, and ANA may each contribute significantly to respective cerebral pools. In contrast, QUIN, KYNA, and 3-HANA cross the blood-brain barrier poorly, and therefore are not expected to contribute significantly to brain pools under normal conditions.read more
Citations
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Journal ArticleDOI
Metabolismo do triptofano em transtornos mentais: um enfoque na esquizofrenia
Michelle S. Carvalho,Camila M. Yonamine,Caroline Dal Mas,Dayane Felix Silva Nunes,Mirian A. F. Hayashi +4 more
TL;DR: O triptofano (TRP) is an aminoacido essencial, encontrado no plasma principalmente ligado a albumina, e com apenas uma pequena fracao encontradada na forma livre as mentioned in this paper.
Journal ArticleDOI
The metabolomics approach revealed a distinctive metabolomics pattern associated with hyperthyroidism treatment
Malak A. Jaber,Hicham Benabdelkamel,Lina A. Dahabiyeh,Afshan Masood,Reem H. AlMalki,Mohthash Musambil,Assim A. Alfadda,Anas M. Abdel Rahman +7 more
TL;DR: In this paper , the authors used untargeted metabolomics to explore the potential pathways and metabolic patterns associated with hyperthyroidism treatment using liquid chromatography-high-resolution mass spectrometry.
Journal ArticleDOI
Is Poor Lithium Response in Individuals with Bipolar Disorder Associated with Increased Degradation of Tryptophan along the Kynurenine Pathway? Results of an Exploratory Study
Frederike T. Fellendorf,Mirko Manchia,Alessio Squassina,Claudia Pisanu,Stefano Dall'Acqua,Stefania Sut,Sofia Nasini,Donatella Congiu,Eva Z. Reininghaus,Mario Garzilli,Beatrice Guiso,Federico Suprani,Pasquale Paribello,Vittoria Pulcinelli,Maria Novella Iaselli,Ilaria Pinna,G. Somaini,Laura Arru,Carolina Corrias,Federica Pinna,Bernardo Carpiniello,Stefano Comai +21 more
TL;DR: The data indicate that lithium exerts anti-inflammatory effects by inhibiting indoleamine-2,3-dioxygenase (IDO)-1 activity and strengthens the assumption that the clinical drug response might be associated with biochemical processes.
Book ChapterDOI
The Role of Kynurenine Pathway Metabolites in Neuropsychiatric Disorders
TL;DR: The following chapter will review both preclinical and clinical studies where kynurenine and its most abundant metabolic products were evaluated in relation to a range of highly prevalent neuropsychiatric disorders including schizophrenia, depression, and ADHD.
Journal ArticleDOI
Tryptophan Challenge in Healthy Controls and People with Schizophrenia: Acute Effects on Plasma Levels of Kynurenine, Kynurenic Acid and 5-Hydroxyindoleacetic Acid
Korrapati V. Sathyasaikumar,Francesca M. Notarangelo,Deanna L. Kelly,Laura M. Rowland,Stephanie M. Hare,Shuo Chen,Chen Mo,Robert W. Buchanan,Robert Schwarcz +8 more
TL;DR: Measurements of circulating metabolites following an acute TRP challenge may be informative for assessing the in vivo efficacy of drugs that modulate the neosynthesis of KYNA and other products of TRP degradation.
References
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Journal ArticleDOI
Quinolinic acid: an endogenous metabolite that produces axon-sparing lesions in rat brain
TL;DR: Intracerebral injection of the neuroexcitatory tryptophan metabolite, quinolinic acid, has behavioral, neurochemical and neuropathological consequences reminiscent of those of exogenous excitotoxins, such as kainic and ibotenic acids.
Journal ArticleDOI
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Journal ArticleDOI
Amino acid assignment to one of three blood-brain barrier amino acid carriers
William H. Oldendorf,John Szabo +1 more
TL;DR: Affinity for a basic amino acid carrier system was demonstrated for arginine, ornithine, and lysine and a third, low-capacity independent carrier system transporting aspartic and glutamic acids was demonstrated.
Journal ArticleDOI
An in situ brain perfusion technique to study cerebrovascular transport in the rat
TL;DR: The in situ brain perfusion technique is a sensitive new method to study cerebrovascular transfer in the rat and permits absolute control of perfusate composition.