Sphingosine 1-phosphate lyase inhibition by 2-acetyl-4-(tetrahydroxybutyl)imidazole (THI) under conditions of vitamin B6 deficiency. 2015

Mamoru Ohtoyo, and Masakazu Tamura, and Nobuo Machinaga, and Fumihito Muro, and Ryuji Hashimoto
New Modality Research Laboratories, R&D Division, Daiichi Sankyo Co., Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo, 140-8710, Japan, otoyo.mamoru.v7@daiichisankyo.co.jp.

Caramel food colorant 2-acetyl-4-(tetrahydroxybutyl)imidazole (THI) causes lymphopenia in animals through sphingosine 1-phosphate lyase (SPL) inhibition. However, this mechanism of action is partly still controversial because THI did not inhibit SPL in vitro either in cell-free or in cell-based systems. It is thought that the in vitro experimental conditions which have been used so far were not suitable for the evaluation of SPL inhibition, especially in case of cell-based experiments. We speculated that the key factor might be the coenzyme pyridoxal 5'-phosphate (PLP), an active form of vitamin B6 (VB6), because media used in cell-based assays usually contain an excess amount of VB6 which leads to the activation of SPL. By the use of VB6-deficient culture medium, we could regulate apo- (without PLP) and holo- (with PLP) SPL enzyme in cultured cells, resulting in the successful detection of SPL inhibition by THI. Although the observed inhibitory effect was not as strong as that of 4-deoxypyridoxine (a VB6 analog SPL inhibitor), these findings may be useful for further understanding the mechanism of action of THI.

UI MeSH Term Description Entries
D007093 Imidazoles Compounds containing 1,3-diazole, a five membered aromatic ring containing two nitrogen atoms separated by one of the carbons. Chemically reduced ones include IMIDAZOLINES and IMIDAZOLIDINES. Distinguish from 1,2-diazole (PYRAZOLES).
D011732 Pyridoxal Phosphate This is the active form of VITAMIN B 6 serving as a coenzyme for synthesis of amino acids, neurotransmitters (serotonin, norepinephrine), sphingolipids, aminolevulinic acid. During transamination of amino acids, pyridoxal phosphate is transiently converted into pyridoxamine phosphate (PYRIDOXAMINE). Pyridoxal 5-Phosphate,Pyridoxal-P,Phosphate, Pyridoxal,Pyridoxal 5 Phosphate,Pyridoxal P
D002241 Carbohydrates A class of organic compounds composed of carbon, hydrogen, and oxygen in a ratio of Cn(H2O)n. The largest class of organic compounds, including STARCH; GLYCOGEN; CELLULOSE; POLYSACCHARIDES; and simple MONOSACCHARIDES. Carbohydrate
D000446 Aldehyde-Lyases Enzymes that catalyze a reverse aldol condensation. A molecule containing a hydroxyl group and a carbonyl group is cleaved at a C-C bond to produce two smaller molecules (ALDEHYDES or KETONES). EC 4.1.2. Aldolases,Aldehyde Lyases
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D026681 Vitamin B 6 Deficiency A nutritional condition produced by a deficiency of VITAMIN B 6 in the diet, characterized by dermatitis, glossitis, cheilosis, and stomatitis. Marked deficiency causes irritability, weakness, depression, dizziness, peripheral neuropathy, and seizures. In infants and children typical manifestations are diarrhea, anemia, and seizures. Deficiency can be caused by certain medications, such as isoniazid. Pyridoxine Deficiency,Deficiency, Pyridoxine,Deficiency, Vitamin B 6,Deficiency, Vitamin B6,Vitamin B6 Deficiency,Vitamin Deficiency, B6,B6 Deficiencies, Vitamin,B6 Deficiency, Vitamin,B6 Vitamin Deficiencies,B6 Vitamin Deficiency,Deficiencies, B6 Vitamin,Deficiencies, Vitamin B6,Deficiency, B6 Vitamin,Vitamin B6 Deficiencies,Vitamin Deficiencies, B6

Related Publications

Mamoru Ohtoyo, and Masakazu Tamura, and Nobuo Machinaga, and Fumihito Muro, and Ryuji Hashimoto
April 2015, Journal of enzyme inhibition and medicinal chemistry,
Mamoru Ohtoyo, and Masakazu Tamura, and Nobuo Machinaga, and Fumihito Muro, and Ryuji Hashimoto
August 1991, Clinical and experimental immunology,
Mamoru Ohtoyo, and Masakazu Tamura, and Nobuo Machinaga, and Fumihito Muro, and Ryuji Hashimoto
August 1992, Thymus,
Mamoru Ohtoyo, and Masakazu Tamura, and Nobuo Machinaga, and Fumihito Muro, and Ryuji Hashimoto
May 2010, Xenobiotica; the fate of foreign compounds in biological systems,
Mamoru Ohtoyo, and Masakazu Tamura, and Nobuo Machinaga, and Fumihito Muro, and Ryuji Hashimoto
July 2017, Naunyn-Schmiedeberg's archives of pharmacology,
Mamoru Ohtoyo, and Masakazu Tamura, and Nobuo Machinaga, and Fumihito Muro, and Ryuji Hashimoto
November 2020, Journal of cellular and molecular medicine,
Mamoru Ohtoyo, and Masakazu Tamura, and Nobuo Machinaga, and Fumihito Muro, and Ryuji Hashimoto
September 2020, Journal of inherited metabolic disease,
Mamoru Ohtoyo, and Masakazu Tamura, and Nobuo Machinaga, and Fumihito Muro, and Ryuji Hashimoto
August 2013, Journal of agricultural and food chemistry,
Mamoru Ohtoyo, and Masakazu Tamura, and Nobuo Machinaga, and Fumihito Muro, and Ryuji Hashimoto
January 2000, Methods in enzymology,
Mamoru Ohtoyo, and Masakazu Tamura, and Nobuo Machinaga, and Fumihito Muro, and Ryuji Hashimoto
May 1992, International journal of immunopharmacology,
Copied contents to your clipboard!