Modification of myo-inositol monophosphatase by the arginine-specific reagent phenylglyoxal.
myo-Inositol monophosphatase is inhibited by the arginine-specific reagent phenylglyoxal. The rate of inactivation is decreased in the presence of Pi, a competitive inhibitor of the enzyme. The effect of Pi is dependent on the presence of Mg2+, but is unaffected by Li+, an uncompetitive inhibitor. In the absence of Mg2+, the substrate, Ins(1)P, binds to the enzyme but is not converted into products, and affords only a small degree of protection against inactivation by phenylglyoxal. Li+ had no further effect under these conditions, but in the presence of Mg2+ caused a marked potentiation of the protective effect of substrate alone. In the absence of substrate, Li+ had no effect on activation by phenylglyoxal. Incorporation of 14C-labelled phenylglyoxal showed that inactivation was associated with modification of a single arginine residue per monomer in the dimeric enzyme. These findings support a mechanism in which Li+ inhibits monophosphatase by trapping a phosphorylated enzyme intermediate and preventing its hydrolysis.
Jackson
R G
RG
Merck Sharp & Dohme Research Laboratories, Neuroscience Research Centre, Harlow, Essex, U.K.
Gee
N S
NS
Ragan
C I
CI
D000447:Aldehydes / Q000494:pharmacology*; D000818:Animals; D001120:Arginine; D001921:Brain / Q000201:enzymology; D002417:Cattle; D002712:Chlorides / Q000494:pharmacology; D004492:Edetic Acid / Q000494:pharmacology; D007700:Kinetics; D008094:Lithium / Q000494:pharmacology; D018021:Lithium Chloride; D015636:Magnesium Chloride / Q000494:pharmacology; D008433:Mathematics; D008962:Models, Theoretical; D010658:Phenylglyoxal / Q000494:pharmacology*; D010710:Phosphates / Q000494:pharmacology; D010744:Phosphoric Monoester Hydrolases / Q000037:antagonists & inhibitors* / Q000302:isolation & purification
D000447:Aldehydes; D002712:Chlorides; D010710:Phosphates; D015636:Magnesium Chloride; D001120:Arginine; D008094:Lithium; D004492:Edetic Acid; D010744:Phosphoric Monoester Hydrolases; C021822:myo-inositol-1 (or 4)-monophosphatase; D018021:Lithium Chloride; D010658:Phenylglyoxal