Aluminum affects phosphoinositide hydrolysis by phosphoinositidase C.
A single phosphoinositidase C (PIC) activity has been purified 500-fold from bovine heart cytosol to a specific activity of 3 mumol phosphatidylinositol (Ptdlns) hydrolyzed/(min.mg protein). The enzyme required Ca2+ for the hydrolysis of polyphosphoinositides or Ptdlns; PIC activity was saturable at micromolar free Ca2+ concentrations with an apparent KCa of 230nM. None of the multivalent cations tested could effectively substitute for Ca2+ in the activation of PIC, although several ions inhibited PIC activity in the presence of Ca2+. AlCl3 had a differential effect on PIC activity, stimulating Ptdlns hydrolysis while inhibiting Ptdlns-(4,5)P2 hydrolysis in a concentration-dependent manner from 1-100 microM. The effect of AlCl3 was attributed to the free ion, Al3+. Complexation of Al3+ with phosphate, citrate, fluoride, or hydroxide could block the stimulatory effect on Ptdlns hydrolysis. Only fluoride or hydroxide could partially reverse the inhibition of Ptdlns-(4,5)P2 hydrolysis by AlCl3.
McDonald
L J
LJ
Department of Biological Sciences, Wright State University, Dayton, OH 45435.
Mamrack
M D
MD
D000535:Aluminum / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000502:physiology; D002417:Cattle; D003600:Cytosol / Q000201:enzymology; D006868:Hydrolysis; D009206:Myocardium / Q000201:enzymology; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D010716:Phosphatidylinositols / Q000378:metabolism*; D010727:Phosphoric Diester Hydrolases / Q000302:isolation & purification / Q000502:physiology*
D010716:Phosphatidylinositols; D000535:Aluminum; D010727:Phosphoric Diester Hydrolases; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D002118:Calcium