Mittal C K, Harrell W B, Mehta C S
Division of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, Texas Southern University, Houston 77004, USA.
Mol Cell Biochem. 1995 Aug-Sep;149-150:263-5. doi: 10.1007/BF01076586.
This study was designed to evaluate the in vitro effects of transition heavy metal cations on activity of constitutive isoform of nitric oxide synthase (cNOS) in rat brain. NOS activity was determined in the cytosolic fractions of rat cerebral hemispheres by conversion of 3H-L-arginine to 3H-L-citrulline. Different concentrations of mercury (Hg2+), nickel (Ni2+), manganese (Mn2+), zinc (Zn2+), cadmium (Cd2+), lead (Pd2+) and calcium (Ca2+) were tested on NOS activity. While all the cations caused inhibition, there were differences in the apparent inhibition constants (Ki) among the cations. With the exception of calcium ion no other cation required preincubation with the enzyme preparation. These results indicate that while calcium ion modulate cNOS activity at regulatory site(s), inhibitory influence of toxic heavy metal cations may be exerted on the catalytic site(s) either by direct binding to it or by interfering with the electron transfer during catalysis.
本研究旨在评估过渡重金属阳离子对大鼠脑组织中组成型一氧化氮合酶（cNOS）活性的体外影响。通过将3H-L-精氨酸转化为3H-L-瓜氨酸，测定大鼠大脑半球胞质部分的NOS活性。测试了不同浓度的汞（Hg2+）、镍（Ni2+）、锰（Mn2+）、锌（Zn2+）、镉（Cd2+）、铅（Pd2+）和钙（Ca2+）对NOS活性的影响。虽然所有阳离子均导致抑制，但各阳离子的表观抑制常数（Ki）存在差异。除钙离子外，其他阳离子均无需与酶制剂预孵育。这些结果表明，虽然钙离子在调节位点调节cNOS活性，但有毒重金属阳离子的抑制作用可能是通过直接结合催化位点或在催化过程中干扰电子传递而施加于催化位点的。
