Figure 2

Blood-brain barrier endothelial cells metabolization of Pyr-sulf and Cat-sulf. (a) Putative pathways and enzymes that could be involved in endothelial metabolism into novel phenolic compounds. Proposed metabolization route of the compounds was designed based on canonical enzymatic reactions described in KEGG (Kyoto Encyclopedia of Genes and Genomes). ARS - Arylsulfatase; GST - Glutathione S-transferase; GGT - Gamma glutamyl transferase; AP - Aminopeptidase; Cys-NAT – Cysteine N-acetyl transferase; COMT - Catechol O-methyl transferase; UDPG – UDP-Glucuronosyl transferase. Relative quantification (peak areas) of the novel phenolic metabolites appearing in upper (grey) and lower (black) compartments along time after addition of (b–f) Pyr-sulf or (g–j) Cat-sulf in upper compartment, namely (b) Glutathionyl-pyrogallol, (c) Acetylcysteine-pyrogallol, (d) 2-O-methylcatechol-O-sulfate, (e) Glutathionyl-catechol and (f) Acetylcysteine-2-O-methylcatechol, (g) 2-O-methylcatechol, (h) Catechol-1-O-β-D-glucoronic acid, (i) Glutathionyl-2-O-methylcatechol, and (j) Acetylcysteine-2-O-methylcatechol. Note: the compound Acetylcysteine-2-O-methylcatechol was detected in both samples (panels’ f and j).