TY - JOUR
T1 - Glutathione metabolism by γ-glutamyltranspeptidase leads to lipid peroxidation
T2 - Characterization of the system and relevance to hepatocarcinogenesis
AU - Stark, Avishay Abraham
AU - Zeiger, Errol
AU - Pagano, Dennis A.
N1 - Funding Information:
We wish to thank Dr R.Langenbach, NIEHS, for many helpful discussions. A considerable part of this work was performed while A.-A.S. was a visiting scientist at the NIEHS. This work was supported in part by a project grant from the Israd Cancer Research Fund.
PY - 1993/2
Y1 - 1993/2
N2 - Glutathione (GSH)-driven lipid peroxidation (LPO) in vitro was catalyzed by γ-glutamyltranspeptidase (GGT; EC 2.3.2.2.). The reaction required iron, iron chelators and oxygen, was accelerated by glycylglycine (gly)2, a GGT enhancer, and was inhibited by the GGT inhibitors serine-borate and acivicin. LPO occurred at rat plasma concentrations of GSH and transferrin, and in the presence of putative physiological chelators such as citrate and ADP. GSH-driven LPO was inhibited by butylated hydroxytoluene, but not by catalase, peroxidase or superoxide dismutase. These results suggest that metabolism of GSH initiated by GGT may lead to oxidative damage. Such oxidative damage may be induced in vivo by GSH in proximity to GGT-rich preneoplastic foci in rat liver.
AB - Glutathione (GSH)-driven lipid peroxidation (LPO) in vitro was catalyzed by γ-glutamyltranspeptidase (GGT; EC 2.3.2.2.). The reaction required iron, iron chelators and oxygen, was accelerated by glycylglycine (gly)2, a GGT enhancer, and was inhibited by the GGT inhibitors serine-borate and acivicin. LPO occurred at rat plasma concentrations of GSH and transferrin, and in the presence of putative physiological chelators such as citrate and ADP. GSH-driven LPO was inhibited by butylated hydroxytoluene, but not by catalase, peroxidase or superoxide dismutase. These results suggest that metabolism of GSH initiated by GGT may lead to oxidative damage. Such oxidative damage may be induced in vivo by GSH in proximity to GGT-rich preneoplastic foci in rat liver.
UR - http://www.scopus.com/inward/record.url?scp=0027229929&partnerID=8YFLogxK
U2 - 10.1093/carcin/14.2.183
DO - 10.1093/carcin/14.2.183
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AN - SCOPUS:0027229929
SN - 0143-3334
VL - 14
SP - 183
EP - 189
JO - Carcinogenesis
JF - Carcinogenesis
IS - 2
ER -