Amino Acids

, Volume 42, Issue 5, pp 1967–1973 | Cite as

An investigation into possible xenobiotic–endobiotic inter-relationships involving the amino acid analogue drug, S-carboxymethyl-l-cysteine and plasma amino acids in humans

  • Glyn B. Steventon
  • Stephen C. Mitchell
  • Santigo Angulo
  • Coral Barbas
Original Article


The amino acid derivative, S-carboxymethyl-l-cysteine, is an anti-oxidant agent extensively employed as adjunctive therapy in the treatment of human pulmonary conditions. A major biotransformation route of this drug, which displays considerable variation in capacity in man, involves the oxidation of the sulfide moiety to the inactive S-oxide metabolite. Previous observations have indicated that fasted plasma l-cysteine concentrations and fasted plasma l-cysteine/free inorganic sulfate ratios were correlated with the degree of sulfoxidation of this drug and that these particular parameters may be used as endobiotic biomarkers for this xenobiotic metabolism. It has been proposed also that the enzyme, cysteine dioxygenase, was responsible for the drug sulfoxidation. Further in this theme, the degree of S-oxidation of S-carboxymethyl-l-cysteine in 100 human volunteers was investigated with respect to it potential correlation with fasted plasma amino acid concentrations. Extensive statistical analyses showed no significant associations or relationships between the degree of drug S-oxidation and fasted plasma amino acid concentrations, especially with respect to the sulfur-containing compounds, methionine, l-cysteine, l-cysteine sulfinic acid, taurine and free inorganic sulfate, also the derived ratios of l-cysteine/l-cysteine sulfinic acid and l-cysteine/free inorganic sulfate. It was concluded that plasma amino acid levels or derived ratios cannot be employed to predict the degree of S-oxidation of S-carboxymethyl-l-cysteine (or vice versa) and that it is doubtful if the enzyme, cysteine dioxygenase, has any involvement in the metabolism of this drug.


Metabolomics S-oxidation S-carboxymethyl-l-cysteine l-Cysteine/sulfate ratio Cysteine dioxygenase 



GBS would like to thank the Wellcome Trust, UK, Parkinson’s Disease Society, UK, Bloomer Trust, UK, and the Motor Neurone Disease Association, UK for funding this project.


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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Glyn B. Steventon
    • 1
  • Stephen C. Mitchell
    • 2
  • Santigo Angulo
    • 3
  • Coral Barbas
    • 3
  1. 1.Clinical Medicine Division, Postgraduate Medical SchoolUniversity of SurreySurreyUK
  2. 2.Biomolecular Medicine, Department of Surgery and Cancer, Faculty of MedicineImperial College LondonLondonUK
  3. 3.Faculty of PharmacySan Pablo-CEU UniversityMadridSpain

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