Activation of (Na+, K+)-ATPase by nanomolar concentrations of GM1 ganglioside.
GM1 ganglioside binding to the crude mitochondrial fraction of rat brain and its effect on (Na+, K+)-ATPase were studied, the following results being obtained: (a) the binding process followed a biphasic kinetics with a break at 50 nM-GM1; GM1 at concentrations below the break was stably associated, while over the break it was loosely associated; (b) stably bound GM1 activated (Na+, K+)-ATPase up to a maximum of 43%; (c) the activation was dependent upon the amount of bound GM1 and was highest at the critical concentration of 20 pmol bound GM1 X mg protein-1; (d) loosely bound GM1 suppressed the activating effect on (Na+, K+)-ATPase elicited by firmly bound GM1; (e) GM1-activated (Na+, K+)-ATPase had the same pH optimum and apparent Km (for ATP) as normal (Na+, K+)-ATPase but a greater apparent Vmax; (f) under identical binding conditions (2 h, 37 degrees C, with 40 nM substance) all tested gangliosides (GM1, GD1a, GD1b, GT1b) activated (Na+, K+)-ATPase (from 26-43%); NeuNAc, sodium dodecylsulphate, sulphatide and cerebroside had only a very slight effect. It is suggested that the ganglioside activation of (Na+-K+)-ATPase is a specific phenomenon not related to the amphiphilic and ionic properties of gangliosides, but due to modifications of the membrane lipid environment surrounding the enzyme.
D000818:Animals; D001921:Brain / Q000201:enzymology*; D004789:Enzyme Activation; D005677:G(M1) Ganglioside / Q000494:pharmacology*; D005732:Gangliosides / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D008928:Mitochondria / Q000201:enzymology*; D051381:Rats; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D013329:Structure-Activity Relationship
D005732:Gangliosides; D005677:G(M1) Ganglioside; D000254:Sodium-Potassium-Exchanging ATPase