A synthesis and quantification method for endogenous metabolites dimethylguanidino valeric acid
Abstract Dimethylguanidino valeric acid (DMGV) is a group of endogenous metabolites derived from arginine-containing proteins and is associated with several metabolic disorders. Latest studies have identified the stereoisomers of DMGV: asymmetric dimethylguanidino valeric acid (ADGV) and symmetric d...
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Nature Portfolio
2025-04-01
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| Online Access: | https://doi.org/10.1038/s41598-025-94932-z |
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| author | Yueyuan Han Jiahui Wang Qianling Xiong Dingyue Jiang Zhenhua Zhu Li Hui Mu Wang Yixue Qiao Yi Li Lanlan Han Yan Liu Ken Cheng |
| author_facet | Yueyuan Han Jiahui Wang Qianling Xiong Dingyue Jiang Zhenhua Zhu Li Hui Mu Wang Yixue Qiao Yi Li Lanlan Han Yan Liu Ken Cheng |
| author_sort | Yueyuan Han |
| collection | DOAJ |
| description | Abstract Dimethylguanidino valeric acid (DMGV) is a group of endogenous metabolites derived from arginine-containing proteins and is associated with several metabolic disorders. Latest studies have identified the stereoisomers of DMGV: asymmetric dimethylguanidino valeric acid (ADGV) and symmetric dimethylguanidino valeric acid (SDGV), which are derived from asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA), respectively. However, the lack of commercial standards has hampered research into the molecular mechanisms of DMGV and its potential clinical application as biomarkers. Reported chemical synthesis methods have low yields and require specialized chemical synthesis skills and apparatus. Therefore, we aimed to develop a practical and efficient method to synthesize DMGV stereoisomers and determine their precise concentration profile in healthy subjects. A novel biocatalytic method for synthesizing DMGV using alanine-glyoxylate aminotransferase 2 (AGXT2) was developed. A metabolite panel including eight DMGV-related metabolites was also established for human plasma samples using HPLC-MS/MS, and its performance was comprehensively evaluated, especially in terms of quantitative sensitivity, precision and accuracy. Compared with the reported chemical synthesis methods, the biocatalytic approach demonstrates superior yield, conversion rate, and product purity, while being easy to implement in biological laboratories. The established DMGV quantification method has been well validated and successfully applied to measure the contents of these metabolites, especially the concentration profile of ADGV in the plasma of healthy individuals. To sum up, this study provides an efficient and practical biocatalytic approach for DMGV synthesis and determines the levels of DMGV in healthy subjects. These findings will undoubtedly promote future mechanistic studies of DMGV and its future clinical applications. |
| format | Article |
| id | doaj-art-302caea377644de2be726f75f9fd8b1d |
| institution | DOAJ |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-302caea377644de2be726f75f9fd8b1d2025-08-20T03:07:40ZengNature PortfolioScientific Reports2045-23222025-04-0115111110.1038/s41598-025-94932-zA synthesis and quantification method for endogenous metabolites dimethylguanidino valeric acidYueyuan Han0Jiahui Wang1Qianling Xiong2Dingyue Jiang3Zhenhua Zhu4Li Hui5Mu Wang6Yixue Qiao7Yi Li8Lanlan Han9Yan Liu10Ken Cheng11Wisdom Lake of Pharmacy, Xi’an Jiaotong-Liverpool UniversityWisdom Lake of Pharmacy, Xi’an Jiaotong-Liverpool UniversityGuangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-sen UniversityWisdom Lake of Pharmacy, Xi’an Jiaotong-Liverpool UniversityResearch Center of Biological Psychiatry, Suzhou Guangji Hospital, Medical College of Soochow UniversityResearch Center of Biological Psychiatry, Suzhou Guangji Hospital, Medical College of Soochow UniversityWisdom Lake of Pharmacy, Xi’an Jiaotong-Liverpool UniversityWisdom Lake of Pharmacy, Xi’an Jiaotong-Liverpool UniversityWisdom Lake of Pharmacy, Xi’an Jiaotong-Liverpool UniversityDepartment of Biosciences and Bioinformatics, School of Science, Xi’an Jiaotong-Liverpool UniversityGuangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-sen UniversityWisdom Lake of Pharmacy, Xi’an Jiaotong-Liverpool UniversityAbstract Dimethylguanidino valeric acid (DMGV) is a group of endogenous metabolites derived from arginine-containing proteins and is associated with several metabolic disorders. Latest studies have identified the stereoisomers of DMGV: asymmetric dimethylguanidino valeric acid (ADGV) and symmetric dimethylguanidino valeric acid (SDGV), which are derived from asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA), respectively. However, the lack of commercial standards has hampered research into the molecular mechanisms of DMGV and its potential clinical application as biomarkers. Reported chemical synthesis methods have low yields and require specialized chemical synthesis skills and apparatus. Therefore, we aimed to develop a practical and efficient method to synthesize DMGV stereoisomers and determine their precise concentration profile in healthy subjects. A novel biocatalytic method for synthesizing DMGV using alanine-glyoxylate aminotransferase 2 (AGXT2) was developed. A metabolite panel including eight DMGV-related metabolites was also established for human plasma samples using HPLC-MS/MS, and its performance was comprehensively evaluated, especially in terms of quantitative sensitivity, precision and accuracy. Compared with the reported chemical synthesis methods, the biocatalytic approach demonstrates superior yield, conversion rate, and product purity, while being easy to implement in biological laboratories. The established DMGV quantification method has been well validated and successfully applied to measure the contents of these metabolites, especially the concentration profile of ADGV in the plasma of healthy individuals. To sum up, this study provides an efficient and practical biocatalytic approach for DMGV synthesis and determines the levels of DMGV in healthy subjects. These findings will undoubtedly promote future mechanistic studies of DMGV and its future clinical applications.https://doi.org/10.1038/s41598-025-94932-zADGVBiosynthesis of DMGVConcentration profile of DMGVHPLC-MS/MSSDGV |
| spellingShingle | Yueyuan Han Jiahui Wang Qianling Xiong Dingyue Jiang Zhenhua Zhu Li Hui Mu Wang Yixue Qiao Yi Li Lanlan Han Yan Liu Ken Cheng A synthesis and quantification method for endogenous metabolites dimethylguanidino valeric acid Scientific Reports ADGV Biosynthesis of DMGV Concentration profile of DMGV HPLC-MS/MS SDGV |
| title | A synthesis and quantification method for endogenous metabolites dimethylguanidino valeric acid |
| title_full | A synthesis and quantification method for endogenous metabolites dimethylguanidino valeric acid |
| title_fullStr | A synthesis and quantification method for endogenous metabolites dimethylguanidino valeric acid |
| title_full_unstemmed | A synthesis and quantification method for endogenous metabolites dimethylguanidino valeric acid |
| title_short | A synthesis and quantification method for endogenous metabolites dimethylguanidino valeric acid |
| title_sort | synthesis and quantification method for endogenous metabolites dimethylguanidino valeric acid |
| topic | ADGV Biosynthesis of DMGV Concentration profile of DMGV HPLC-MS/MS SDGV |
| url | https://doi.org/10.1038/s41598-025-94932-z |
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