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
This study was designed to examine if platinum nanoparticles have an activity similar to mitochondrial complex I, NADH:ubiquinone oxidoreductase. Platinum nanoparticles were prepared by a citrate reduction of H(2)PtCl(6) and protected by citrate itself and pectin (CP-Pt). Time- and dose-dependent decreases in NADH and a time-dependent increase in NAD(+) were observed in the presence of 50 microM CP-Pt; these observations were made using a spectrophotometric method in which the maximum absorption spectra at 340 and 260 nm were used for NADH and NAD(+), respectively. The required platinum concentration in CP-Pt to achieve a 50% oxidation of NADH for 3h was approximately 20 microM, and this NADH oxidation did not require oxygen as an electron acceptor. We also verified NAD(+) formation using an NAD(+)/NADH quantification kit. The absorption peak shift from 278 to 284 nm of 2,3-dimethoxy-5-methyl-6-(3-methyl-2-butenyl)-1,4-benzoquinone (CoQ(1)) was observed by incubating CoQ(1) with CP-Pt in an aqueous buffer. A further analysis with HPLC revealed the reduction of CoQ(1) to CoQ(1)H(2) by CP-Pt. As a whole, platinum nanoparticles have an NADH:ubiquinone oxidoreductase-like activity. This suggests that platinum nanoparticles are a potential medicinal substance for oxidative stress diseases with suppressed mitochondrial complex I.