Madawala, Romanthi and Banks, Jasmine L. and Hancock, Sarah E. and Quek, Lake-Ee and Turner, Nigel and Wu, Lindsay E. (2025) CD38 mediates nicotinamide mononucleotide base exchange to yield nicotinic acid mononucleotide. Journal of Biological Chemistry, 301 (3). p. 108248. ISSN 00219258
Full text not available from this repository.Abstract
Nicotinamide mononucleotide (NMN) is a widely investigated metabolic precursor to the prominent enzyme cofactor NAD(+), where it is assumed that delivery of this compound results in its direct incorporation into NAD(+)via the canonical salvage/recycling pathway. Surprisingly, treatment with this salvage pathway intermediate leads to increases in nicotinic acid mononucleotide (NaMN) and nicotinic acid adenine dinucleotide, two members of the Preiss-Handler/de novo pathways. In mammals, these pathways are not known to intersect prior to the production of NAD(+). Here, we show that the cell surface enzyme CD38 can mediate a base-exchange reaction on NMN, whereby the nicotinamide ring is exchanged with a free nicotinic acid to yield the Preiss-Handler/de novo pathway intermediate NaMN, with in vivo small molecule inhibition of CD38 abolishing the NMN-induced increase in NaMN and nicotinic acid adenine dinucleotide. Together, these data demonstrate a new mechanism by which the salvage pathway and Preiss-Handler/de novo pathways can exchange intermediates in mammalian NAD(+) biosynthesis.
| Item Type: | Article |
|---|---|
| Subjects: | R Medicine > R Medicine (General) |
| Depositing User: | Repository Administrator |
| Date Deposited: | 05 May 2025 06:40 |
| Last Modified: | 05 May 2025 06:40 |
| URI: | https://eprints.victorchang.edu.au/id/eprint/1689 |
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