The Use of p-Aminobenzoic Acid as a Probe Substance for the Targeted Profiling of Glycine Conjugation.
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.
Focus Area: Human Metabolomics, North-West University, Potchefstroom 2531, North-West, South Africa.
Carla
C
Nortje
Focus Area: Human Metabolomics, North-West University, Potchefstroom 2531, North-West, South Africa.
Rencia
R
van der Sluis
Focus Area: Human Metabolomics, North-West University, Potchefstroom 2531, North-West, South Africa.
Alberdina Aike
AA
van Dijk
Focus Area: Human Metabolomics, North-West University, Potchefstroom 2531, North-West, South Africa. Lardus.Erasmus@NWU.ac.za.
Elardus
E
Erasmus
D010129:4-Aminobenzoic Acid / Q000008:administration & dosage* / Q000652:urine; D005998:Glycine / Q000378:metabolism*; D006626:Hippurates / Q000378:metabolism; D006801:Humans; D015335:Molecular Probes
D006626:Hippurates; D015335:Molecular Probes; C030514:hippuric acid; D005998:Glycine; D010129:4-Aminobenzoic Acid
Glycine conjugation; glycine N-acyltransferase; p-Aminobenzoic acid; p-Aminohippuric acid