Metabolic Pathway of Cis-UCA Upon UVB Exposure Using ¹H NMR Spectroscopy, Molecular Docking, and Cell Viability of Human Keratinocytes (HaCaT) Cell Lines

This study investigates the metabolic pathway of cis-urocanic acid (cis-UCA) upon UVB exposure, using NMR spectroscopy, molecular docking, and cell viability assays with human keratinocytes (HaCaT). The research reveals that cis-UCA can react with reactive sulphur species (RSS) donors without the involvement of the glutathione-S-transferase (GST) enzyme, leading to the formation of a new compound, 4-imidazoleacrylic acid-3-thiol. The study also finds that the formation of glutathione and cysteine conjugates can occur non-enzymatically, challenging the previously proposed GST-dependent pathway. Molecular docking shows that the glutathione conjugate has a higher binding affinity with GST than sulforaphane, suggesting a regulatory role. In vitro studies demonstrate that UVB exposure with cis-UCA reduces cell viability, but the presence of sulphide donors mitigates this toxicity, highlighting their protective role. This research provides new insights into cis-UCA metabolism and suggests an alternative RSS-driven pathway, impacting our understanding of UCA's role in UVB-induced skin reactions.