Gamma-glutamyl transpeptidase does not act as a cystine transporter in brain microvessels.
Gamma-glutamyl transpeptidase (GGTP) is highly enriched in blood-brain barrier (BBB) microvessels. According to the most cited hypothesis its functional role is amino acid transport across the BBB. To test this hypothesis the influence of GGTP inhibition on cystine uptake was measured in isolated brain microvessels. Adult porcine brain microvessels were enzymatically isolated, resulting in an enrichment of GGTP from 3 to 85 U/mg protein. The inhibitors 0.1 mM AT-125 combined with 20 mM hippurate reduced the GGPT enzyme activity by more than 98%. However this inhibition did not influence the uptake of [35S]-cystine, which is the substrate with the highest affinity in the GGTP-reaction. Instead increased glutathione (GSH) levels and elevated [35S] release were found. These results show that GGTP does not mediate the transport of cystine into brain microvessels in vitro and suggest that GGTP plays a role in cellular GSH metabolism.
Department of Pediatric Oncology and Hematology, University of Münster, Germany.
J E
JE
Wolff
G
G
Münstermann
K
K
Grebenkämper
M
M
Erben
D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D001812:Blood-Brain Barrier / Q000187:drug effects; D001921:Brain / Q000098:blood supply; D002560:Cerebrovascular Circulation / Q000502:physiology*; D003553:Cystine / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D007555:Isoxazoles / Q000494:pharmacology; D007700:Kinetics; D008833:Microcirculation / Q000378:metabolism*; D013552:Swine; D005723:gamma-Glutamyltransferase / Q000037:antagonists & inhibitors / Q000378:metabolism*
D000596:Amino Acids; D004791:Enzyme Inhibitors; D007555:Isoxazoles; D003553:Cystine; D005723:gamma-Glutamyltransferase; C006303:acivicin