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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
Author(s) -
Baumann Tim,
Bergmann Sophia,
SchmidtRose Thomas,
Max Heiner,
Martin Annette,
Enthaler Bernd,
Terstegen Lara,
Schweiger Dorothea,
Kalbacher Hubert,
Wenck Horst,
Jedlitschky Gabriele,
Jovanovic Zorica
Publication year - 2014
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/exd.12354
Subject(s) - glutathione , biochemistry , chemistry , glutathione s transferase , atp binding cassette transporter , transferase , transporter , vesicle , enzyme , gene , membrane
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 .