Moriyama Y, Patel V, Ueda I, Futai M
Department of Biochemistry and Organic Chemistry, Osaka University, Japan.
Biochem Biophys Res Commun. 1993 Oct 29;196(2):699-706. doi: 10.1006/bbrc.1993.2306.
Vacuolar-type H(+)-ATPase from adrenal chromaffin granules was found to be sensitive to omeprazole, a known gastric H+/K(+)-ATPase inhibitor, the concentration required for 50% inhibition being 80 microM freshly-prepared and 12 microM acid-treated reagent. ATP and ADP protected the enzyme from inhibition by omeprazole. The activity of the inhibited enzyme was restored by the addition of reduced glutathione. Omeprazole protected the enzyme from inhibition by N-ethylmaleimide and its binding to the subunit A. As subunit A has a nucleotide binding site(s) and as a cysteine residue is involved in the inhibition by N-ethylmaleimide, these results suggested that the two sulfhydryl reagents bind to the same cysteine residue near the nucleotide binding domain in the subunit A, resulting in inactivation of vacuolar-type H(+)-ATPase.
研究发现，肾上腺嗜铬颗粒中的液泡型H(+) -ATP酶对奥美拉唑敏感，奥美拉唑是一种已知的胃H+/K(+) -ATP酶抑制剂，50%抑制所需浓度对于新制备的试剂为80微摩尔，酸处理后的试剂为12微摩尔。ATP和ADP可保护该酶免受奥美拉唑的抑制。加入还原型谷胱甘肽可恢复被抑制酶的活性。奥美拉唑可保护该酶免受N -乙基马来酰亚胺的抑制及其与A亚基的结合。由于A亚基有一个核苷酸结合位点，且一个半胱氨酸残基参与N -乙基马来酰亚胺的抑制作用，这些结果表明这两种巯基试剂与A亚基中核苷酸结合结构域附近的同一个半胱氨酸残基结合，导致液泡型H(+) -ATP酶失活。
