Metabolism of inositol 1- and 4-monophosphates in HL60 promyelocytic leukaemia cells.
The metabolism of inositol 1- and 4-monophosphates in HL60 promyelocytic leukaemia cells was studied. LiCl, BeCl2 and NaF inhibited the hydrolysis of both monophosphates with half maximal inhibition occurring at 1.2 mM, 0.3 microM, 0.25 mM (Ins 1P) and 0.14 mM, 0.56 microM, 0.28 mM (Ins 4P) respectively. Lithium was an uncompetitive inhibitor with respect to both substrates. Ins 4P inhibited the hydrolysis of Ins 1P in a concentration dependent manner, suggesting that it acts as a competing substrate for the same enzyme. Half maximal inhibition occurred at 120 microM Ins 4P. The lithium sensitive activity responsible for the metabolism of both monophosphates was present in a soluble fraction made from the cells. Taken together these data suggest that Ins 1P and Ins 4P are hydrolysed by a single soluble enzyme activity which is sensitive to inhibition by lithium, beryllium and fluoride.
Creba
J A
JA
Research Department II, ICI Pharmaceuticals, Macclesfield, Cheshire, U.K.
Carey
F
F
Frearson
J
J
McCulloch
A
A
D001608:Beryllium / Q000494:pharmacology; D005459:Fluorides / Q000494:pharmacology; D006801:Humans; D007295:Inositol Phosphates / Q000378:metabolism*; D007700:Kinetics; D015473:Leukemia, Promyelocytic, Acute; D008094:Lithium / Q000494:pharmacology; D010744:Phosphoric Monoester Hydrolases / Q000037:antagonists & inhibitors / Q000378:metabolism; D014407:Tumor Cells, Cultured
D007295:Inositol Phosphates; C002647:inositol 1-phosphate; C045537:inositol 4-phosphate; D008094:Lithium; D010744:Phosphoric Monoester Hydrolases; C021822:myo-inositol-1 (or 4)-monophosphatase; D001608:Beryllium; D005459:Fluorides