摘要：SummaryIn 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 B3partially regulates plasma NAM and NAM-derived metabolites, but not their tissue levels. We found that NADde novosynthesis 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 the 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.Graphical abstractDisplay OmittedHighlights•Different pools of nicotinamide (NAM) exist in the organism•NADde novosynthesis and dietetic NAD precursors regulate the plasma NAM pool•CD38 in endothelial and immune cells regulates tissue NAM, but not plasma NAM pool•Tissue NAM used for M-NAM synthesis is a CD38-independent poolBiological sciences; Biochemistry; Molecular biology; Immunology
