| First Author | Zeidler JD | Year | 2022 |
| Journal | iScience | Volume | 25 |
| Issue | 11 | Pages | 105431 |
| PubMed ID | 36388973 | Mgi Jnum | J:352989 |
| Mgi Id | MGI:7386484 | Doi | 10.1016/j.isci.2022.105431 |
| Citation | Zeidler JD, et al. (2022) Endogenous metabolism in endothelial and immune cells generates most of the tissue vitamin B3 (nicotinamide). iScience 25(11):105431 |
| abstractText | In mammals, nicotinamide (NAM) is the primary NAD precursor available in circulation, a signaling molecule, and a precursor for methyl-nicotinamide (M-NAM) synthesis. However, our knowledge about how the body regulates tissue NAM levels is still limited. Here we demonstrate that dietary vitamin B(3) partially regulates plasma NAM and NAM-derived metabolites, but not their tissue levels. We found that NAD de novo synthesis from tryptophan contributes to plasma and tissue NAM, likely by providing substrates for NAD-degrading enzymes. We also demonstrate that tissue NAM is mainly generated by endogenous metabolism and that the NADase CD38 is the main enzyme that produces tissue NAM. Tissue-specific CD38-floxed mice revealed that CD38 activity on endothelial and immune cells is the major contributor to tissue steady-state levels of NAM in tissues like spleen and heart. Our findings uncover the presence of different pools of NAM in the body and a central role for CD38 in regulating tissue NAM levels. |
