The binding of lithium and of anionic metabolites to phosphoglucomutase.

Intercept inhibition of rabbit-muscle phosphoglucomutase (alpha-D-glucose-1,6-bisphosphate: alpha-D-glucose-1-phosphate phosphotransferase, EC 2.7.5.1) produced by several nucleotide diphosphates and compounds related to coenzyme A was re-examined in order to re-evaluate an earlier suggestion that this enzyme has an allosteric regulatory site. However, in all cases intercept inhibition constants were much larger than those previously reported, and in all but two cases were too large to assess in the assay system, i.e., were greater than 10 mM. Most of the intercept inhibition previously observed apparently was caused by the use of the Li+ salts of inhibitors. Thus, Li+ binds competitively with the natural activator, Mg2+, and in the presence of glucose phosphates binds almost as well as Mg2+: Kd approximately 10 micrometer. The observation that glucose phosphates bind to the Li+ complex of phosphoglucomutase some 900 times more tenaciously than to the corresponding Mg2+ complex could provide a partial rationale for the lack of reactivity of the Le+ form of the enzyme. Attempts to verify the dimeric structure of phosphoglucomutase that was previously reported also produced negative results.