| Literature DB >> 27185637 |
Mamoru Ohtoyo1, Nobuo Machinaga2, Ryotaku Inoue3, Katsunobu Hagihara4, Hiroshi Yuita5, Masakazu Tamura6, Ryuji Hashimoto6, Jun Chiba2, Fumihito Muro7, Jun Watanabe2, Yoshimasa Kobayashi8, Koji Abe4, Yasuo Kita9, Miyuki Nagasaki10, Takaichi Shimozato10.
Abstract
Caramel color is widely used in the food industry, and its many variations are generally considered to be safe. It has been known for a long time that THI (2-acetyl-4-(tetrahydroxybutyl)imidazole), a component of caramel color III, causes lymphopenia in animals through sphingosine 1-phosphate (S1P) lyase (S1PL) inhibition. However, this mechanism of action has not been fully validated because THI does not inhibit S1PL in vitro. To reconcile this situation, we examined molecular details of THI mechanism of action using "smaller" THI derivatives. We identified a bioactive derivative, A6770, which has the same lymphopenic effect as THI via S1PL inhibition. In the case of A6770 we observe this effect both in vitro and in vivo, and demonstrate that A6770 is phosphorylated and inhibits S1PL in the same way as 4-deoxypyridoxine. In addition, A6770 was detected in rat plasma following oral administration of THI, suggesting that A6770 is a key metabolic intermediate of THI.Entities:
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Year: 2016 PMID： 27185637 DOI： 10.1016/j.chembiol.2016.04.007
Source DB: PubMed Journal: Cell Chem Biol ISSN： 2451-9448 Impact factor: 8.116