The use of p-aminobenzoic acid as a probe substance for the targeted profiling of glycine conjugation
Date
2016Author
Nortje, Carla
Van der Sluis, Rencia
Van Dijk, Alberdina Aike
Erasmus, Elardus
Metadata
Show full item recordAbstract
Glycine conjugation facilitates the metabolism of toxic aromatic acids, capable of disrupting mitochondrial integrity. Owing to the high exposure to toxic substrates, characterization of individual glycine conjugation capacity, and its regulatory factors has become increasingly important. Aspirin and benzoate have been employed for this purpose; however, adverse reactions, aspirin intolerance, and Reye's syndrome in children are substantial drawbacks. The goal of this study was to investigate p-aminobenzoic acid (PABA) as an alternative glycine conjugation probe. Ten human volunteers participated in a PABA challenge test, and p-aminohippuric acid (PAHA), p-acetamidobenzoic acid, and p-acetamidohippuric acid were quantified in urine. The glycine N-acyltransferase gene of the volunteers was also screened for two polymorphisms associated with normal and increased enzyme activity. All of the individuals were homozygous for increased enzyme activity, but excretion of PAHA varied significantly (16–56%, hippurate ratio). The intricacies of PABA metabolism revealed possible limiting factors and the potential of PABA as an indicator of Phase 0 biotransformation
URI
http://hdl.handle.net/10394/18916https://doi.org/10.1002/jbt.21772
https://onlinelibrary.wiley.com/doi/abs/10.1002/jbt.21772