title: Histone 2A stimulates glucose-6-phosphatase activity by permeabilization of liver microsomes.
abstract: Histone 2A increases glucose-6-phosphatase activity in liver microsomes. The effect has been attributed either to the conformational change of the enzyme, or to the permeabilization of microsomal membrane that allows the free access of substrate to the intraluminal glucose-6-phosphatase catalytic site. The aim of the present study was the critical reinvestigation of the mechanism of action of histone 2A. It has been found that the dose-effect curve of histone 2A is different from that of detergents and resembles that of the pore-forming alamethicin. Inhibitory effects of EGTA on glucose-6-phosphatase activity previously reported in histone 2A-treated microsomes have been also found in alamethicin-permeabilized vesicles. The effect of EGTA cannot therefore simply be an antagonization of the effect of histone 2A. Histone 2A stimulates the activity of another latent microsomal enzyme, UDP-glucuronosyltransferase, which has an intraluminal catalytic site. Finally, histone 2A renders microsomal vesicles permeable to non-permeant compounds. Taken together, the results demonstrate that histone 2A stimulates glucose-6-phosphatase activity by permeabilizing the microsomal membrane.
authors.affiliation: Dipartimento di Fisiopatologia e Medicina Sperimentale, University of Siena, 53100 Siena, Italy.
authors.forename: Angelo
authors.initials: A
authors.lastname: Benedetti
authors.forename: Rosella
authors.initials: R
authors.lastname: Fulceri
authors.forename: Bernard B
authors.initials: BB
authors.lastname: Allan
authors.forename: Pamela
authors.initials: P
authors.lastname: Houston
authors.forename: Andrey L
authors.initials: AL
authors.lastname: Sukhodub
authors.forename: Paola
authors.initials: P
authors.lastname: Marcolongo
authors.forename: Brian
authors.initials: B
authors.lastname: Ethell
authors.forename: Brian
authors.initials: B
authors.lastname: Burchell
authors.forename: Ann
authors.initials: A
authors.lastname: Burchell
mesh_terms: D000408:Alamethicin / Q000494:pharmacology; D000818:Animals; D002219:Carbamates / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D005952:Glucose-6-Phosphatase / Q000187:drug effects / Q000378:metabolism*; D005960:Glucosides / Q000494:pharmacology; D014453:Glucuronosyltransferase / Q000187:drug effects / Q000378:metabolism; D006657:Histones / Q000378:metabolism* / Q000494:pharmacology; D007425:Intracellular Membranes; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D010539:Permeability; D011092:Polyethylene Glycols / Q000494:pharmacology; D051381:Rats
chemical_list: D002219:Carbamates; D005960:Glucosides; D006657:Histones; C060539:6-O-(N-heptylcarbamoyl)methylglucoside; D000408:Alamethicin; D011092:Polyethylene Glycols; C005092:lubrol; D004533:Egtazic Acid; D014453:Glucuronosyltransferase; D005952:Glucose-6-Phosphatase