title: Inhibition of steady-state mitochondrial ATP synthesis by bicarbonate, an activating anion of ATP hydrolysis.
abstract: Bicarbonate, an activating anion of ATP hydrolysis, inhibited ATP synthesis coupled to succinate oxidation in beef heart submitochondrial particles but diminished the lag time and increased the steady-state velocity of the (32)Pi-ATP exchange reaction. The latter effects exclude the possibility that bicarbonate is inducing an intrinsic uncoupling between ATP hydrolysis and proton translocation at the level of F(1)F(o) ATPase. The inhibition of ATP synthesis was competitive with respect to ADP at low fixed [Pi], mixed at high [Pi] and non-competitive towards Pi at any fixed [ADP]. From these results we can conclude that (i) bicarbonate does not bind to a Pi site in the mitochondrial F(1); (ii) it competes with the binding of ADP to a low-affinity site, likely the low-affinity non-catalytic nucleotide binding site. It is postulated that bicarbonate stimulates ATP hydrolysis and inhibits ATP synthesis by modulating the relative affinities of the catalytic site for ATP and ADP.
authors.affiliation: Departamento de Química Biológica, Area Biofísica, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Suipacha 531, (S2002LRK) Rosario, Argentina.
authors.forename: A F
authors.initials: AF
authors.lastname: Lodeyro
authors.forename: N B
authors.initials: NB
authors.lastname: Calcaterra
authors.forename: O A
authors.initials: OA
authors.lastname: Roveri
mesh_terms: D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D002417:Cattle; D006868:Hydrolysis / Q000187:drug effects; D008929:Mitochondria, Heart / Q000378:metabolism*; D010710:Phosphates / Q000737:chemistry; D006180:Proton-Translocating ATPases / Q000378:metabolism; D017693:Sodium Bicarbonate / Q000494:pharmacology*
chemical_list: D010710:Phosphates; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D017693:Sodium Bicarbonate; D006180:Proton-Translocating ATPases