Studies on the L-2-hydroxy-acid oxidase 2 catalyzed metabolism of S-mandelic acid and its analogues |
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| Affiliation: | 1. Laboratory of Signal Transduction, Department of Cell Biology, Institute for Virus Research, Kyoto University, 53 Shogoin-Kawaharacho, Sakyo-ku, Kyoto, Kyoto 606-8507, Japan;2. Laboratory of Virolution, Experimental Research Center for Infectious Diseases, Institute for Virus Research, Kyoto University, 53 Shogoin-Kawaharacho, Sakyo-ku, Kyoto, Kyoto 606-8507, Japan;3. Department of Molecular Life Science, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa 259-1193, Japan;4. Center for Human Evolution Modeling Research, Primate Research Institute, Kyoto University, Inuyama, Aichi 484-8506, Japan;1. Department of Nutrition and Food Hygiene, School of Public Health, Harbin Medical University, 150081 Harbin, China;2. Department of Epidemiology and Health Statistics & Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Medical University, 350122 Fuzhou, China;3. Songhuajiang Community Health Service Center, Prevention and Health Care Department, the Fourth Hospital of Harbin Medical University, 150080 Harbin, China;4. Department of Nutrition and Food Hygiene, School of Public Health, Hainan Medical University, 570102 Haikou, China;5. College of Bioinformatics Science and Technology, Harbin Medical University, 150081 Harbin, China;6. Training Center for Students Innovation and Entrepreneurship Education, Harbin Medical University, 150081 Harbin, China;7. Imaging Center, Harbin Medical University Cancer Hospital, 150081 Harbin, China;8. Shenzhen Bao''an District Central Hospital, Huangtian Community Health Service Center, 518126 Shenzhen, China;9. Department of Nutrition, Taikang Ningbo Hospital, 315101 Ningbo, China |
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| Abstract: | Mandelic acid (MA) is generally used as a biomarker of the exposure of styrene, which is classified as a class of hazardous environmental pollutants, and also used as an important chiral intermediate in pharmaceutical industry. The previous studies have found the excretion of phenylglyoxylic acid (PGA) in human and rat, a metabolite of MA, was mainly from S-MA rather than R-MA. The metabolic mechanism, however, is not clear. In order to explore the possible metabolic mechanism, the enzyme types involved in the stereoselectivity metabolism of MA were firstly studied, and then human and rat long-chain 2-hydroxy-acid oxidase 2 (HAO2) were recombinantly expressed to study the metabolic profiles of S-MA and its analogues. The results indicated that HAO2 might catalyze the stereoselectivity metabolism of S-MA in rats. Human HAO2 (hHAO2) and rat HAO2 (rHAO2) isozymes β1 and β2 were successfully cloned and expressed with high purity and good enzyme activities. The enzyme kinetic profiles of these enzymes were different for S-MA and analogues. The order of catalytic efficiency for hHAO2 and rHAO2, however, was reverse. It might be relevance to the difference in active amino acid residues and loop 4 in human and rat L-2-hydroxy acid oxidase isozyme B crystal structures. |
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| Keywords: | Mandelic acid Long-chain 2-hydroxy-acid oxidase 2 Stereoselectivity metabolism Mandelic acid analogues Cloning and expression Species difference |
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