L-2-oxothiazolidine-4-carboxylate supplementation in murine gamma-GT deficiency.
gamma-glutamyl transpeptidase (gamma-GT) deficiency in GGT(enu1) mice is associated with glutathionemia, glutathionuria, growth retardation, infertility, lethargy, cataracts, and shortened life span. Total liver glutathione (GSH) content is significantly reduced in gamma-GT-deficient mice due to chronic excessive GSH loss. Oral supplementation of GGT(enu1) mice with L-2-oxothiazolidine-4-carboxylate (OTZ), a cysteine prodrug, led to partial restoration of liver GSH content. The growth, physical appearance, and behavior of gamma-GT-deficient mice were substantially improved following OTZ supplementation. Tissue GSH deficiency is the proximate cause of the phenotypic abnormalities associated with murine gamma-GT deficiency.
Held
Patrice
P
Departments of Pediatrics and Molecular and Medical Genetics, Oregon Health and Sciences University, 707 SW Gaines Road, Portland, OR 97239, USA.
Harding
Cary O
CO
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D019587:Dietary Supplements; D005838:Genotype; D005978:Glutathione / Q000378:metabolism*; D006130:Growth Disorders / Q000201:enzymology*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D051379:Mice; D018345:Mice, Knockout; D011761:Pyrrolidonecarboxylic Acid; D012098:Reproduction / Q000187:drug effects; D013844:Thiazoles / Q000494:pharmacology*; D053778:Thiazolidines; D005723:gamma-Glutamyltransferase / Q000172:deficiency* / Q000378:metabolism*
D013844:Thiazoles; D053778:Thiazolidines; D005723:gamma-Glutamyltransferase; D005978:Glutathione; D011761:Pyrrolidonecarboxylic Acid; C029536:2-oxothiazolidine-4-carboxylic acid