Matsubara Aya, Tanno Haruki, Amekura Sakiko, Iida Sayaka, Yamamoto Yorihiro, Fujisawa Akio
School of Bioscience and Biotechnology, Tokyo University of Technology, 1404-1 Katakura, Hachioji, Tokyo 192-0982, Japan.
J Clin Biochem Nutr. 2024 Mar;74(2):113-118. doi: 10.3164/jcbn.23-67. Epub 2023 Oct 3.
Uric acid is an adequate and endogenous probe for identifying reactive oxygen or nitrogen species generated because its oxidation products are specific to reacted reactive oxygen or nitrogen species. Recently, we identified 5--carboxyimino-6--chloroaminopyrimidine-2,4(3)-dione as a hypochlorite-specific oxidation product. 5--carboxyimino-6--chloroaminopyrimidine-2,4(3)-dione was anticipated to be a biomarker for hypochlorite production . However, while it was stable in aqueous solution at weak acidic and alkaline pH (6.0-8.0), it was unstable in human plasma. In this study, we found that 5--carboxyimino-6--chloroaminopyrimidine-2,4(3)-dione rapidly reacted with thiol compounds such as cysteine and glutathione to yield 5--carboxyimino-6-aminopyrimidine-2,4(3)-dione, which was stable in human plasma unlike 5--carboxyimino-6--chloroaminopyrimidine-2,4(3)-dione. 5--carboxyimino-6-aminopyrimidine-2,4(3)-dione was produced upon uric acid degradation during myeloperoxidase-induced uric acid oxidation and lipopolysaccharide-induced pseudo-inflammation in collected 2,4(3)-dione has potential as a marker for hypochlorite production .
尿酸是一种合适的内源性探针，可用于识别所产生的活性氧或氮物种，因为其氧化产物对反应生成的活性氧或氮物种具有特异性。最近，我们鉴定出5-羧基亚氨基-6-氯氨基嘧啶-2,4(3)-二酮是次氯酸盐特异性氧化产物。5-羧基亚氨基-6-氯氨基嘧啶-2,4(3)-二酮有望成为次氯酸盐生成的生物标志物。然而，尽管它在弱酸性和碱性pH值（6.0 - 8.0）的水溶液中稳定，但在人血浆中不稳定。在本研究中，我们发现5-羧基亚氨基-6-氯氨基嘧啶-2,4(3)-二酮能与半胱氨酸和谷胱甘肽等硫醇化合物迅速反应，生成5-羧基亚氨基-6-氨基嘧啶-2,4(3)-二酮，后者在人血浆中比5-羧基亚氨基-6-氯氨基嘧啶-2,4(3)-二酮更稳定。5-羧基亚氨基-6-氨基嘧啶-2,4(3)-二酮是在髓过氧化物酶诱导的尿酸氧化和脂多糖诱导的伪炎症过程中尿酸降解时产生的。2,4(3)-二酮有潜力作为次氯酸盐生成的标志物。
