Phenylalanine hydroxylase: possible involvement in the S-oxidation of S-carboxymethyl-l-cysteine

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Activated phenylalanine 4-monooxygenase, phenylalanine hydroxylase (PAH), is known to be involved in the S-oxidation of a number of sulfide compounds. One of these compounds, S-carboxymethyl-l-cysteine (SCMC), is currently used for the treatment of chronic obstructive pulmonary disease and otitis media with effusion as a mucolytic agent, and the S-oxides are the major metabolites found in urine. However, the enzyme catalyzing the S-oxidation of SCMC has yet to be identified. Here we report on the role of nonactivated phenylalanine 4-monooxygenase activity in rat liver cytosol in the S-oxidation of SCMC. Linearity of the enzyme assays was seen for both time (0–16min) and cytosolic protein concentration (0.1–0.5mg/ml). The calculated Km and Vmax values for the formation of SCMC (S) S-oxide were 3.92±0.15mM and 1.10±0.12nmol SCMC (S) S-oxide formed/mg protein/min, respectively. The calculated Km and Vmax values for the formation of SCMC (R) S-oxide were 9.18±1.13mM and 0.46±0.11nmol SCMC (R) S-oxide formed/mg protein/min, respectively. These results indicate that in the female Wistar rat, nonactivated PAH showed a stereospecific preference for the formation of the (S) S-oxide metabolite of SCMC against the (R) S-oxide metabolite of SCMC.