title: Gamma-glutamyl transpeptidase inhibition suppresses milk protein synthesis in isolated ovine mammary cells.
abstract: The membrane spanning enzyme gamma-glutamyl transpeptidase (gamma-GT; EC 2.3.2.2) catalyses the breakdown of the tripeptide glutathione and uses free amino acids (AA) to form gamma-glutamyl transpeptidase (GT) AA that become transported into cells and converted back into free AA. gamma-Glutamyl transpeptidase activity has been shown to be important for mammary AA uptake in rodent systems, and while gamma-GT activity is high in lactating bovine mammary tissue, the role of this enzyme in milk protein synthesis of the ruminant has not been defined. The present study shows that gamma-GT activity in the ovine mammary gland, like that of rodents, increases during pregnancy and peaks early in lactation. Acivicin, a well-known inhibitor of gamma-GT, decreased gamma-GT activity in acini isolated from the ovine mammary gland and did not have secondary toxicity effects on cell viability or the uptake of radiolabeled amino-isobutyric acid. Isolated ovine acini were incubated in the presence of radiolabeled leucine, and incorporation of label into secreted protein increased during incubation. Incubation of acini with acivicin decreased milk protein secretion by 75%, indicating that gamma-GT plays an important role in milk protein production in the ruminant. Acivicin did not inhibit secretion of specific caseins but caused a global decrease in individual proteins suggesting that gamma-GT may be responsible for providing a complement of AA for milk protein synthesis.
authors.affiliation: AgResearch Limited, New Zealand.
authors.forename: S L
authors.initials: SL
authors.lastname: Johnston
authors.forename: K E
authors.initials: KE
authors.lastname: Kitson
authors.forename: J W
authors.initials: JW
authors.lastname: Tweedie
authors.forename: S R
authors.initials: SR
authors.lastname: Davis
authors.forename: J
authors.initials: J
authors.lastname: Lee
mesh_terms: D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D007555:Isoxazoles / Q000494:pharmacology; D007774:Lactation; D008321:Mammary Glands, Animal / Q000378:metabolism*; D008894:Milk Proteins / Q000096:biosynthesis* / Q000378:metabolism; D011247:Pregnancy; D012756:Sheep / Q000378:metabolism*; D005723:gamma-Glutamyltransferase / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D007555:Isoxazoles; D008894:Milk Proteins; D005723:gamma-Glutamyltransferase; C006303:acivicin