RESUMEN
Nicotinamide riboside (NR) is one of the orally bioavailable NAD+ precursors and has been demonstrated to exhibit beneficial effects against aging and aging-associated diseases. However, the metabolic pathway of NR in vivo is not yet fully understood. Here, we demonstrate that orally administered NR increases NAD+ level via two different pathways. In the early phase, NR was directly absorbed and contributed to NAD+ generation through the NR salvage pathway, while in the late phase, NR was hydrolyzed to nicotinamide (NAM) by bone marrow stromal cell antigen 1 (BST1), and was further metabolized by the gut microbiota to nicotinic acid, contributing to generate NAD+ through the Preiss-Handler pathway. Furthermore, we report BST1 has a base-exchange activity against both NR and nicotinic acid riboside (NAR) to generate NAR and NR, respectively, connecting amidated and deamidated pathways. Thus, we conclude that BST1 plays a dual role as glycohydrolase and base-exchange enzyme during oral NR supplementation.
Asunto(s)
ADP-Ribosil Ciclasa/metabolismo , Antígenos CD/metabolismo , Glicósido Hidrolasas/metabolismo , Niacinamida/análogos & derivados , Compuestos de Piridinio/farmacocinética , Células A549 , ADP-Ribosil Ciclasa/genética , Administración Oral , Envejecimiento/efectos de los fármacos , Animales , Antígenos CD/genética , Suplementos Dietéticos , Proteínas Ligadas a GPI/genética , Proteínas Ligadas a GPI/metabolismo , Microbioma Gastrointestinal , Glicósido Hidrolasas/genética , Humanos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiología , Intestino Delgado/metabolismo , Intestino Delgado/microbiología , Ratones , Ratones Noqueados , Niacina/metabolismo , Niacinamida/administración & dosificación , Niacinamida/metabolismo , Niacinamida/farmacocinética , Pentosiltransferasa/genética , Pentosiltransferasa/metabolismo , Compuestos de Piridinio/administración & dosificaciónRESUMEN
A one-step conversion of 3-aryl-3-(2-aminophenyl)-1-propyn-3-ols into quinoline-2(1H)-thiones and quinoline-2(1H)-selones was achieved only by treating the substrates with n-butyllithium and either elemental sulfur or selenium, respectively. The reactions were assumed to proceed through an intramolecular nucleophilic attack of the neighboring amino group to the plausible in situ generated reactive species related to chalcogenoketenes. The subsequent mCPBA oxidation of quinoline-2(1H)-selones afforded quinolin-2(1H)-ones in high yields.