RESUMO
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.
Assuntos
ADP-Ribosil Ciclase/metabolismo , Antígenos CD/metabolismo , Glicosídeo Hidrolases/metabolismo , Niacinamida/análogos & derivados , Compostos de Piridínio/farmacocinética , Células A549 , ADP-Ribosil Ciclase/genética , Administração Oral , Envelhecimento/efeitos dos fármacos , Animais , Antígenos CD/genética , Suplementos Nutricionais , Proteínas Ligadas por GPI/genética , Proteínas Ligadas por GPI/metabolismo , Microbioma Gastrointestinal , Glicosídeo Hidrolases/genética , Humanos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiologia , Intestino Delgado/metabolismo , Intestino Delgado/microbiologia , Camundongos , Camundongos Knockout , Niacina/metabolismo , Niacinamida/administração & dosagem , Niacinamida/metabolismo , Niacinamida/farmacocinética , Pentosiltransferases/genética , Pentosiltransferases/metabolismo , Compostos de Piridínio/administração & dosagemRESUMO
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.