Moffett J R, Blinder K L, Venkateshan C N, Namboodiri M A
Department of Biology, Georgetown University, 37th & O Sts. N.W., Washington, DC 20057-1229, USA.
Cell Tissue Res. 1998 Sep;293(3):525-34. doi: 10.1007/s004410051145.
Quinolinate is a tryptophan metabolite and an intermediary in nicotinamide adenine dinucleotide (NAD+) synthesis in hepatocytes. Kynurenine is an upstream metabolite in the same biochemical pathway. Under normal physiological conditions, kynurenine is thought to be produced primarily in the liver as an NAD+ precursor. However, during immune stimulation or inflammation, numerous extrahepatic tissues convert systemic tryptophan to kynurenine, and its concentration subsequently rises dramatically in blood. The fate and role of extrahepatic kynurenine are uncertain. In order to begin addressing this question, the present study was performed to determine which cell types can produce quinolinate from either systemic tryptophan or kynurenine. By using highly specific antibodies to protein-coupled quinolinate, we found that intraperitoneal injections of tryptophan led to increased quinolinate immunoreactivity primarily in hepatocytes, with moderate increases in tissue macrophages and splenic follicles. In contrast, intraperitoneal injections of kynurenine did not result in any significant increase in hepatocyte quinolinate immunoreactivity, but rather led to dramatic increases in immunoreactivity in tissue macrophages, splenic white pulp, and thymic medulla. These findings suggest that hepatocytes do not make significant use of extracellular kynurenine for quinolinate or NAD+ synthesis, and that, instead, extrahepatic kynurenine is preferentially metabolized by immune cells throughout the body. The possible significance of the preferential metabolism of kynurenine by immune cells during an immune response is discussed.
喹啉酸是一种色氨酸代谢产物，是肝细胞中烟酰胺腺嘌呤二核苷酸（NAD+）合成的中间体。犬尿氨酸是同一生化途径中的上游代谢产物。在正常生理条件下，犬尿氨酸被认为主要在肝脏中作为NAD+前体产生。然而，在免疫刺激或炎症期间，许多肝外组织将全身的色氨酸转化为犬尿氨酸，其浓度随后在血液中急剧上升。肝外犬尿氨酸的命运和作用尚不确定。为了开始解决这个问题，本研究旨在确定哪些细胞类型可以从全身色氨酸或犬尿氨酸产生喹啉酸。通过使用针对蛋白质偶联喹啉酸的高度特异性抗体，我们发现腹腔注射色氨酸主要导致肝细胞中喹啉酸免疫反应性增加，组织巨噬细胞和脾滤泡也有适度增加。相比之下，腹腔注射犬尿氨酸并未导致肝细胞喹啉酸免疫反应性有任何显著增加，而是导致组织巨噬细胞、脾白髓和胸腺髓质中的免疫反应性急剧增加。这些发现表明，肝细胞在喹啉酸或NAD+合成中并未大量利用细胞外犬尿氨酸，相反，肝外犬尿氨酸优先被全身的免疫细胞代谢。本文讨论了免疫反应期间免疫细胞对犬尿氨酸优先代谢的可能意义。
