Potent inhibition of membrane-bound rat intestinal alkaline phosphatase by a new series of phosphate analogues.
The inhibition by phosphonates and phosphate analogues of the alkaline phosphatase activity of rat intestinal brush-border membrane vesicles was studied at pH 7.5 and 30 degrees C. Phenylene-1,3-diphosphonate, 2,6-dinitrophenylphosphonate and phosphonoacetaldehyde were found to be competitive inhibitors, with Ki values in the range 16-80 microM. Adenosine 5'-[beta-thio]diphosphate and adenosine 5'[gamma-thio]triphosphate are also very potent inhibitors, with Ki values of approx. 10 microM. The inhibition produced by these thiophosphates was mainly competitive but with a slight non-competitive element. Adenosine 5'-[beta gamma-imido]triphosphate is also a competitive inhibitor of the alkaline phosphatase, but oxidation of the ribose moiety of this compound with NaIO4 results in an active-site-directed irreversible inhibitor that could be of general use in studies of the mechanism of action of this enzyme.
D000227:Adenine Nucleotides / Q000494:pharmacology; D000469:Alkaline Phosphatase / Q000037:antagonists & inhibitors*; D000818:Animals; D002462:Cell Membrane / Q000201:enzymology*; D066298:In Vitro Techniques; D007421:Intestine, Small / Q000187:drug effects / Q000201:enzymology; D007700:Kinetics; D008871:Microvilli / Q000187:drug effects / Q000201:enzymology*; D009711:Nucleotides / Q000494:pharmacology*; D063065:Organophosphonates / Q000494:pharmacology*; D051381:Rats
D000227:Adenine Nucleotides; D009711:Nucleotides; D063065:Organophosphonates; D000469:Alkaline Phosphatase