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We have previously shown that precursors of odorous components characteristic of axillary sweat are hardly detectable or undetectable in individuals carrying the 538G > A  SNP  in the   ABCC 11  transporter gene. However, it is unclear, whether  ABCC 11 is directly involved in the transport of these compounds. To approach this question, transport of peptide‐conjugated potential precursors of 3‐methyl‐3‐sulfanylhexanol (3M3 SH ), a key determinant of axillary malodour, was measured using membrane vesicles of Sf9 insect cells overexpressing human  ABCC 11. Whilst no  ABCC 11‐mediated transport was detected for the dipeptide precursor Cys‐Gly‐3M3 SH , the glutathione conjugate of 3M3 SH  ( SG ‐3M3 SH ) was robustly taken up by  ABCC 11 at a transport rate of 0.47 pmol/mg/min. Collectively, these results illuminate  SG ‐3M3 SH  as a putative precursor of 3M3 SH , which then may undergo intra‐vesicular maturation to generate Cys‐Gly‐3M3 SH . Critically, the apocrine sweat gland was demonstrated to express  γ ‐glutamyl transferase 1 ( GGT 1) protein, which is known to catalyse the deglutamylation of glutathionyl conjugates. Additionally, we provide evidence that recombinant and isolated hepatic human  GGT 1 is capable of transforming  SG ‐3M3 SH  to Cys‐Gly‐3M3 SH   in vitro . To sum up, we demonstrate that the functionality of  ABCC 11 is likely to play an important role in the generation of axillary malodour. Furthermore, we identify  GGT 1 as a key enzyme involved in the biosynthesis of Cys‐Gly‐3M3 SH .

experimental dermatology

Glutathione‐conjugated sulfanylalkanols are substrates for  ABCC 11 and  γ ‐glutamyl transferase 1: a potential new pathway for the formation of odorant precursors in the apocrine sweat gland