Inhibition of adenosine triphosphatases by gold.
Inhibition of adenosine triphosphatase (ATPase) by chlorauric acid (Au3+) and gold sodium thiomalate (Au+) was studied in dog brain and kidney and in human kidney enzyme preparations. Au3+ indiscriminately affected ouabain-sensitive (Na+ + K+-dependent) ATPase and ouabain-insensitive (Mg2+-dependent) ATPase with concentrations for 50% inhibition (I50) approximately 10(-6) M. The I50 of Au3+ for Na+ + K+ ATPase was several-fold higher in homogenates than in microsomal fractions. The enzyme was protected by bovine serum albumin. Although Au3+ and Au+ were equipotent against Mg2+ ATPase, Au+ inhibited Na+ + K+ ATPase 2 to 3 times more effectively than did Au3+. The inhibitory action of Au3+ (but not Au+) was potentiated by ascorbic acid, suggesting reduction of Au3+ to Au+ by ascorbic acid. The fractional inhibition of Na+ + K+ ATPase by Au3+ or Au+ was not affected by changing concentrations of NaCl, KCl, MgCl2, ATP, and MgATP. Decreasing pH from 8.0 to 6.8 enhanced both Au+ and Au3+ inhibition. We conclude that gold is one of the most potent nonspecific of Na+ + K+ ATPase, with characteristics differing from other metallic inhibitors of this enzyme system.
D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology; D001921:Brain / Q000201:enzymology / Q000378:metabolism; D002712:Chlorides / Q000378:metabolism; D004285:Dogs; D006046:Gold / Q000378:metabolism / Q000494:pharmacology* / Q000506:poisoning; D017612:Gold Compounds; D006052:Gold Sodium Thiomalate / Q000378:metabolism; D007668:Kidney / Q000201:enzymology / Q000378:metabolism / Q000648:ultrastructure; D008861:Microsomes / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors*
D002712:Chlorides; D017612:Gold Compounds; D006052:Gold Sodium Thiomalate; D006046:Gold; C024568:gold tetrachloride, acid; D000254:Sodium-Potassium-Exchanging ATPase; D001205:Ascorbic Acid