Amiloride activation of hepatic microsomal glucose-6-phosphatase; activation of T1?
The mechanism of activation of hepatic microsomal glucose-6-phosphatase (EC 3.1.3.9) in vitro by amiloride has been investigated in both intact and fully disrupted microsomes. The major effect of amiloride is a 4.5-fold reduction in the Km of glucose-6-phosphatase activity in intact diabetic rat liver microsomes. Amiloride also decreased the Km of glucose-6-phosphatase activity in intact liver microsomes isolated from starved rats 2.5-fold. Kinetic calculations, direct enzyme assays and direct transport assays all demonstrated that the site of amiloride action was T1, the hepatic microsomal glucose 6-phosphate transport protein. This is, to our knowledge, the first report of an activation of any of the proteins of the multimeric hepatic microsomal glucose-6-phosphatase complex.
Pears
J
J
Department of Medicine, Ninewells Hospital and Medical School, University of Dundee, U.K.
Jung
R T
RT
Burchell
A
A
D000584:Amiloride / Q000494:pharmacology*; D000818:Animals; D001692:Biological Transport; D002352:Carrier Proteins / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology; D004789:Enzyme Activation / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D005952:Glucose-6-Phosphatase / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D051381:Rats; D011919:Rats, Inbred Strains; D013217:Starvation / Q000201:enzymology
D002352:Carrier Proteins; D000584:Amiloride; D005952:Glucose-6-Phosphatase; D005947:Glucose