Liochev S I, Fridovich I
Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA.
Arch Biochem Biophys. 2001 Apr 15;388(2):281-4. doi: 10.1006/abbi.2001.2296.
Cu,Zn SOD, but not Mn SOD, catalyzes the oxidation of 3-hydroxyanthranilic acid (3-HA) under aerobic conditions. In the absence of O2, the Cu(II) of the enzyme is reduced by 3-HA. One plausible mechanism involves the reduction of the active site Cu(II) to Cu(I), which is then reoxidized by the O2- generated by autoxidation of the anthranilyl or other radicals on the pathway to cinnabarinate. We may call this the superoxide reductase, or SOR, mechanism. Another possibility invokes direct reoxidation of the active site Cu(I) by the anthranilyl, or other organic radicals, or by the peroxyl radicals generated by addition of O2 to these organic radicals. Such oxidations catalyzed by Cu,Zn SOD could account for the deleterious effects of the mutant Cu,Zn SODs associated with familial amyotrophic lateral sclerosis and of the overproduction or overadministration of wild-type Cu,Zn SOD.
铜锌超氧化物歧化酶（Cu,Zn SOD）而非锰超氧化物歧化酶（Mn SOD），在有氧条件下催化3-羟基邻氨基苯甲酸（3-HA）的氧化反应。在无氧条件下，该酶的铜（II）会被3-HA还原。一种可能的机制是活性位点的铜（II）被还原为铜（I），随后铜（I）被邻氨基苯甲酰基或生成朱砂酸途径上的其他自由基自氧化产生的超氧阴离子（O2-）再氧化。我们可将此称为超氧化物还原酶（SOR）机制。另一种可能性是活性位点的铜（I）被邻氨基苯甲酰基或其他有机自由基，或被这些有机自由基与O2加成产生的过氧自由基直接再氧化。由铜锌超氧化物歧化酶催化的此类氧化反应，可能解释了与家族性肌萎缩侧索硬化相关的突变型铜锌超氧化物歧化酶，以及野生型铜锌超氧化物歧化酶过量产生或过量施用所带来的有害影响。
