Drummond G S, Kappas A
Biochem J. 1980 Nov 15;192(2):637-48. doi: 10.1042/bj1920637.
Mn2+ and Zn2+ exhibit a striking ability to block the induction by Sn2+ and Ni2+ of haem oxygenase (EC 1.14.99.3) in kidney. The blocking effects of Mn2+ and Zn2+ were found to be greatest on simultaneous administration, time-dependent when administered up to 8 h before the inducing metal ions, and ineffective when administered as little as 10 min after the inducing metal ions. The decreases in cytochrome P-450 and haem contents and the sequential changes in delta-aminolaevulinate synthase (EC 2.3.1.37) activity that occur concomitant with haem oxygenase induction were largely eliminated with simultaneous or prior treatment with Mn2+ or Zn2+, but not when Mn2+ or Zn2+ was administered after Sn2+ or Ni2+. Mn2+ and Zn2+ did not increase the catabolism of the enzyme in vivo. Zn2+ on simultaneous administration was also able substantially to block the induction of haem oxygenase by Co2+, Cd2+ and Ni2+ in liver. The Zn2+ blockade of Cd2+ induction was examined in detail, and prior or simultaneous administration of Zn2+ was found to be effective in blocking the induction of haem oxygenase and the concomitant decreases in cytochrome P-450 and haem contents, ethylmorphine demethylase activity and the sequential changes in delta-aminolaevulinate synthase activity. Zn2+ administration 10 min or more after Cd2+ was ineffective in preventing the occurrence of these perturbations in haem metabolism. These findings describe a new and striking biological property of Mn2+ and Zn2+, and indicate the existence of significant metal ion interactions in the control of haem metabolism.
锰离子（Mn2+）和锌离子（Zn2+）具有显著能力，可阻断肾中由锡离子（Sn2+）和镍离子（Ni2+）诱导的血红素加氧酶（酶编号：1.14.99.3）。研究发现，Mn2+和Zn2+的阻断作用在同时给药时最为显著；在诱导性金属离子给药前长达8小时给药时呈时间依赖性；而在诱导性金属离子给药后仅10分钟给药则无效。与血红素加氧酶诱导同时发生的细胞色素P - 450和血红素含量降低以及δ-氨基乙酰丙酸合酶（酶编号：2.3.1.37）活性的顺序变化，在同时或预先用Mn2+或Zn2+处理时基本消除，但在Sn2+或Ni2+后给予Mn2+或Zn2+时则未消除。Mn2+和Zn2+在体内并未增加该酶的分解代谢。同时给药时，Zn2+也能显著阻断肝脏中由钴离子（Co2+）、镉离子（Cd2+）和Ni2+诱导的血红素加氧酶。详细研究了Zn2+对Cd2+诱导的阻断作用，发现预先或同时给予Zn2+可有效阻断血红素加氧酶的诱导以及细胞色素P - 450和血红素含量、乙基吗啡脱甲基酶活性的同时降低以及δ-氨基乙酰丙酸合酶活性的顺序变化。在Cd2+给药10分钟或更长时间后给予Zn2+，对于预防血红素代谢中这些紊乱的发生无效。这些发现描述了Mn2+和Zn2+一种新的显著生物学特性，并表明在血红素代谢控制中存在重要的金属离子相互作用。
