Kinetic consequences of the inhibition by ATP of the metabolism of inositol (1,4,5) trisphosphate and inositol (1,3,4,5) tetrakisphosphate in liver. Different effects upon the 3- and 5-phosphatases.
A kinetic analysis was undertaken of the inhibition by 5 mM MgATP of Ins(1,4,5)P3 5-phosphatase in 100,000 g particulate fractions prepared from liver homogenates. The Km for Ins(1,4,5)P3 was increased by 44% (from 16 to 23 microM). The competitive nature of the inhibition was confirmed with a Dixon plot. The effect of MgATP on 5-phosphatase was also studied at physiological concentrations of Ins(1,4,5)P3 and Ins(1,3,4,5)P4 (i.e. 1.5 microM); the rate of substrate hydrolysis was inhibited by over 30%. Ins(1,3,4,5)P4 was also hydrolysed by a 3-phosphatase, but this enzyme was unaffected by 5 mM MgATP. Thus, ATP, by differentially affecting Ins(1,3,4,5)P4 3- and 5-phosphatase, may increase the flux through the futile cycle that interconverts Ins(1,4,5)P3 and Ins(1,3,4,5)P4.
Shears
S B
SB
Inositol Lipid Section, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709.
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D001667:Binding, Competitive; D002851:Chromatography, High Pressure Liquid; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D007295:Inositol Phosphates / Q000378:metabolism*; D000072181:Inositol Polyphosphate 5-Phosphatases; D007700:Kinetics; D008099:Liver / Q000201:enzymology*; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D007295:Inositol Phosphates; C081655:inositol-1,3,4,5-tetrakisphosphate; D015544:Inositol 1,4,5-Trisphosphate; D000255:Adenosine Triphosphate; D010744:Phosphoric Monoester Hydrolases; D000072181:Inositol Polyphosphate 5-Phosphatases