Inhibition of hydrolytic enzymes by gold compounds. I. beta-Glucuronidase and acid phosphatase by sodium tetrachloroaurate (III) and potassium tetrabromoaurate (III).
Purified bovine liver beta-glucuronidase (beta-D-glucuronide glucuronohydrolase, EC 3.2.1.32) and wheat germ acid phosphatase (orthophosphoric monoesterphosphohydrolase, EC 3.1.3.2) were inhibited with freshly dissolved and 24 h aquated tetrahaloaurate (III) compounds. Rate and equilibrium inhibition constants were measured. From this data two acid phosphatases species were observed. Equilibrium inhibition constants ranged from 1 to 12.5 microM for the various gold compounds toward both enzymes. The first order rate constants ranged between 0.005 and 0.04 min.-1 for most reactions with the exception of the fast reacting acid phosphatase which had values as high as 2.6 and 2.8 min.-1. It is observed that the beta-glucuronidase is rapidly inhibited during the equilibrium phase before the more slower reaction covalent bond formation takes place. The acid phosphatases form the covalent bonds more rapidly, especially the faster reacting species suggesting a unique difference in the active site geometry to that of the more slowly reacting species. The tightly bonded gold (III)-enzyme complex is probably the reason for its toxicity and non-anti-inflammatory use as a drug.
Lee
M T
MT
Department of Chemistry, Auburn University, AL 36849-5312.
Ahmed
T
T
Friedman
M E
ME
D000135:Acid Phosphatase / Q000037:antagonists & inhibitors*; D000818:Animals; D001965:Bromides / Q000494:pharmacology*; D002417:Cattle; D002712:Chlorides / Q000494:pharmacology*; D005966:Glucuronidase / Q000037:antagonists & inhibitors* / Q000302:isolation & purification; D006046:Gold / Q000494:pharmacology*; D017612:Gold Compounds; D006867:Hydrolases / Q000037:antagonists & inhibitors*; D007700:Kinetics; D008099:Liver / Q000201:enzymology; D008433:Mathematics
D001965:Bromides; D002712:Chlorides; D017612:Gold Compounds; D006046:Gold; C024568:gold tetrachloride, acid; C037129:gold tetrabromide, acid; D006867:Hydrolases; D000135:Acid Phosphatase; D005966:Glucuronidase