内皮细胞和免疫细胞中的内源性代谢产生了大部分组织维生素B3（烟酰胺）。
Endogenous metabolism in endothelial and immune cells generates most of the tissue vitamin B3 (nicotinamide).
作者信息
Zeidler Julianna D, Chini Claudia C S, Kanamori Karina S, Kashyap Sonu, Espindola-Netto Jair M, Thompson Katie, Warner Gina, Cabral Fernanda S, Peclat Thais R, Gomez Lilian Sales, Lopez Sierra A, Wandersee Miles K, Schoon Renee A, Reid Kimberly, Menzies Keir, Beckedorff Felipe, Reid Joel M, Brachs Sebastian, Meyer Ralph G, Meyer-Ficca Mirella L, Chini Eduardo Nunes
机构信息
Signal Transduction and Molecular Nutrition Laboratory, Kogod Aging Center, Department of Anesthesiology and Perioperative Medicine, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
Department of Anesthesiology and Perioperative Medicine Mayo Clinic, Jacksonville, FL 32224, USA.
出版信息
iScience. 2022 Oct 23;25(11):105431. doi: 10.1016/j.isci.2022.105431. eCollection 2022 Nov 18.
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 partially regulates plasma NAM and NAM-derived metabolites, but not their tissue levels. We found that NAD 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.
在哺乳动物中，烟酰胺（NAM）是循环中可用的主要NAD前体、一种信号分子以及甲基烟酰胺（M-NAM）合成的前体。然而，我们对身体如何调节组织NAM水平的了解仍然有限。在这里，我们证明饮食中的维生素B部分调节血浆NAM和NAM衍生的代谢物，但不调节它们的组织水平。我们发现色氨酸合成NAD有助于血浆和组织中的NAM，可能是通过为NAD降解酶提供底物。我们还证明组织NAM主要由内源性代谢产生，并且NAD酶CD38是产生组织NAM的主要酶。组织特异性CD38基因敲除小鼠显示，内皮细胞和免疫细胞上的CD38活性是脾脏和心脏等组织中组织NAM稳态水平的主要贡献者。我们的研究结果揭示了体内存在不同的NAM池以及CD38在调节组织NAM水平中的核心作用。
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