Effect of oxyanions of the early transition metals on rabbit skeletal muscle phosphorylase

Abstract

The differential effects of the oxyanions of the early transition metals ions V(V), W(VI), and Mo(VI) on the catalytic activity and coenzyme binding of rabbit skeletal muscle phosphorylase are studied. The oligoanions of V(V), W(VI), and Mo(VI) are potent inhibitors of phosphorylase. Kinetic studies revealed that oligovanadates inhibit pyridoxal-reconstituted phosphorylase b by competing with both the substrate, glucose 1-phosphate, and the activator, phosphite, with K1 values of 4 microM and 6 microM, respectively. Oligovanadates in the millimolar concentration range inhibit phosphorylases a and b by competing with glucose 1-phosphate binding. The polymeric decavanadate and paratungstates caused time-dependent inactivation of phosphorylase. Spectral studies with tungstate and phosphorylase b revealed that the inactivation is due to deformation of the coenzyme site. Kinetic studies and the protective effects of substrate and effectors on inactivation and deformation by tungstate or vanadate suggest that deformation and inactivation is caused by a primary binding of the oligoanions at the glucose 1-phosphate site. Nuclear magnetic resonance (NMR) studies of vanadate-phosphorylase complexes and vanadate solutions under different conditions were carried out to ascertain the nature of vanadate ions interacting with functional groups in phosphorylase. The results suggest that decavanadate is the major protein-bound species. NMR studies also showed that guanidino groups react with decavanadate and suggest that arginine residues in phosphorylase are potential functional groups that can interact with decavanadate.(ABSTRACT TRUNCATED AT 250 WORDS)

The binding of vanadium (V) oligoanions to sarcoplasmic reticulum

“…The tetrahedrally [12, 191, are inhibited only by the large octahedrally coordinated decameric vanadium (V) polyanion ; in these systems the monomeric vanadate anion, or its lower tetrahedral polyanionic species are ineffective. In the case of phosphorylase all oligomeric forms are inhibitory, while monomeric vanadate activates the enzyme slightly [20].…”

“…In the case of phosphorylase all oligomeric forms are inhibitory, while monomeric vanadate activates the enzyme slightly [20].…”

“…The tetrahedrally [12, 191, are inhibited only by the large octahedrally coordinated decameric vanadium (V) polyanion ; in these systems the monomeric vanadate anion, or its lower tetrahedral polyanionic species are ineffective. In the case of phosphorylase all oligomeric forms are inhibitory, while monomeric vanadate activates the enzyme slightly [20].Finally the K, of 4 nM for the inhibition of Na, K-ATPase by vanadate [21] strongly argues for monomeric vanadate anion being the inhibitory species; there is no evidence implicating vanadium polymers in the inhibition.In this report we correlate the binding of monovanadate and decavanadate to sarcoplasmic reticulum vesicles with their effects on the crystallization of the Ca2+-ATPase and on the rate of Ca2 +-activated ATP hydrolysis. The results suggest that both monovanadate and decavanadate inhibit the Ca2+-stimulated ATP hydrolysis, but decavanadate is particularly effective in promoting the crystallization of Ca2+-ATPase.…”

Chemical, Biochemical, and Biological Behaviors of Vanadate and Its Oligomers

“…It is presumed that the nanosize clusters of V 10 carrying a number of oxygen atoms in the surface have high affinity to bind with the positively charged domain of a protein (Soman et al 1983). The binding causes conformation change or/and blocks the substrate binding of proteins.…”

Vanadium oxoanions and cAMP-dependent protein kinase: an anti-substrate inhibitor

“…Decavanadate has been found to inhibit adenylate cyclase [25], phosphorylase [26] and fructose-1,6-bisphosphate aldolase [18], as well as the phosphotransferase enzymes hexokinase, adenylate kinase and phosphofructokinase [17]. Interestingly, a non-competitive inhibition pattern is elicited by decavanadate for the hexokinase-catalysed reaction with both ATP and glucose substrates [17].…”