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
Maternal protein restriction during gestation and lactation in the rat results in increased brain levels of kynurenine and kynurenic acid in their adult offspring.
Paula Honório de Melo Martimiano,Paula Honório de Melo Martimiano,Andre Oliveira,Andre Oliveira,Véronique Ferchaud-Roucher,Mikaël Croyal,Audrey Aguesse,Isabelle Grit,Khadija Ouguerram,Sandra Lopes de Souza,Bertrand Kaeffer,Francisco Bolaños-Jiménez +11 more
TL;DR: Results show that early protein deficiency induces selective and long‐lasting changes in brain kynurenine metabolism, which might contribute to the risk of developing psychiatric disorders induced by early malnutrition.
Journal ArticleDOI
Crosstalk between Tryptophan Metabolism via Kynurenine Pathway and Carbohydrate Metabolism in the Context of Cardio-Metabolic Risk-Review.
TL;DR: In this article, the authors discussed the progress in tryptophan metabolism via kynurenine pathway (KP) research, focusing particular attention on the roles in carbohydrate metabolism and its complications in the cardiovascular system.
Journal ArticleDOI
Production of L-tryptophan-derived catabolites in hepatocytes from streptozotocin-induced diabetic rats.
TL;DR: It is suggested that STZ-diabetes mellitus causes augmentations of both l-Kyn and QA generations but not those of PA and Nam in liver, indicating the possibility that the immune and neuronal systems of insulin dependent diabetes mellitus would be influenced by the increased amounts of lKynand QA but not by those ofPA and Nam.
Book ChapterDOI
Amino Acid Transport in Brain
TL;DR: Imbalances in amino acids profoundly influence brain function, as evidenced by the severe irreversible mental retardation that occurs in phenylketonuria and maple-syrup urine syndrome.
BookDOI
Targeting the Broadly Pathogenic Kynurenine Pathway
TL;DR: In this chapter, a broad overview of the kynurenine pathway is provided and the gene regulation of the key enzymes involved are explored.
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
Distinct mediating systems for the transport of neutral amino acids by the ehrlich cell
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.