| RRC ID |
63284
|
| Author |
Yaku K, Palikhe S, Izumi H, Yoshida T, Hikosaka K, Hayat F, Karim M, Iqbal T, Nitta Y, Sato A, Migaud ME, Ishihara K, Mori H, Nakagawa T.
|
| Title |
BST1 regulates nicotinamide riboside metabolism via its glycohydrolase and base-exchange activities.
|
| Journal |
Nat Commun
|
| Abstract |
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.
|
| Volume |
12(1)
|
| Pages |
6767
|
| Published |
2021-11-19
|
| DOI |
10.1038/s41467-021-27080-3
|
| PII |
10.1038/s41467-021-27080-3
|
| PMID |
34799586
|
| PMC |
PMC8604996
|
| MeSH |
A549 Cells
ADP-ribosyl Cyclase / genetics
ADP-ribosyl Cyclase / metabolism*
Administration, Oral
Aging / drug effects
Animals
Antigens, CD / genetics
Antigens, CD / metabolism*
Dietary Supplements
GPI-Linked Proteins / genetics
GPI-Linked Proteins / metabolism
Gastrointestinal Microbiome
Glycoside Hydrolases / genetics
Glycoside Hydrolases / metabolism*
Humans
Intestinal Mucosa / metabolism
Intestinal Mucosa / microbiology
Intestine, Small / metabolism
Intestine, Small / microbiology
Mice
Mice, Knockout
Niacin / metabolism
Niacinamide / administration & dosage
Niacinamide / analogs & derivatives*
Niacinamide / metabolism
Niacinamide / pharmacokinetics
Pentosyltransferases / genetics
Pentosyltransferases / metabolism
Pyridinium Compounds / administration & dosage
Pyridinium Compounds / pharmacokinetics*
|
| IF |
12.121
|
| Resource |
| Human and Animal Cells |
A549(RCB0098)
CACO-2(RCB0988) |
| Mice |
RBRC01462
RBRC02401 |
