Identification of Rat Liver Glucose-3-phosphatase as an Inositol Monophosphatase Inhibited by Lithium

Glucose-3-phosphatase (Glc3Pase) from rat liver has been purified 780-fold with a 4% recovery. The substrate specificity of the purified enzyme agreed with that of inositol monophosphatase (EC 3.1.3.25).d-Glucose 3-phosphate (D-Glc(3)P;Km= 200 μm) was hydrolyzed with an efficiency similar todl-myo-inositol 1-monophosphate (dl-Ins(1)P;Km= 80 μm), since the ratioVmax/Kmwas similar for both substrates. Purification data, coelution of activities, thermal inactivation curves, optimal pH, bivalent cation requirements, inhibition by Li+, molecular weight, and isoelectric pH comparisons supported that the hydrolysis ofd-Glc(3)P anddl-Ins(1)P was catalyzed by a unique phosphohydrolase identified as a hepatic form of the lithium-sensitive inositol monophosphatase. That the hydrolysis ofd-Glc(3)P is a genuine feature of inositol monophosphatases was confirmed because the enzyme purified from bovine brain showed also Glc3Pase activity, and inspection of published 3D models of inositol monophosphatase complexes withd(l)-Ins(1)P ord(l)-Ins(4)P indicated that β(α)-d-Glc(3)P in a pyranose conformation with all (but one) the hydroxy groups in equatorial orientation would fit in the active site as other good substrates do. The results of this work are suggestive of possible relationships between inositol and sugar 3-phosphate metabolism.