Cupp-Sutton Kellye, Ashby Michael T
Department of Chemistry and Biochemistry, University of Oklahoma, Norman, OK 73019, USA.
Antioxidants (Basel). 2021 Oct 20;10(11):1646. doi: 10.3390/antiox10111646.
Lactoperoxidase (LPO, Fe in its resting state in the absence of substrates)-an enzyme secreted from human mammary, salivary, and other mucosal glands-catalyzes the oxidation of thiocyanate (SCN) by hydrogen peroxide (HO) to produce hypothiocyanite (OSCN), which functions as an antimicrobial agent. The accepted catalytic mechanism, called the halogen cycle, comprises a two-electron oxidation of LPO by HO to produce oxoiron(IV) radicals, followed by O-atom transfer to SCN. However, the mechanism does not explain biphasic kinetics and inhibition by HO at low concentration of reducing substrate, conditions that may be biologically relevant. We propose an ordered sequential mechanism in which the order of substrate binding is reversed, first SCN and then HO. The sequence of substrate binding that is described by the halogen cycle mechanism is actually inhibitory.
乳过氧化物酶（LPO，在无底物时处于静止状态的铁）是一种由人乳腺、唾液腺和其他粘膜腺分泌的酶，它催化过氧化氢（HO）将硫氰酸盐（SCN）氧化生成次硫氰酸盐（OSCN），次硫氰酸盐作为一种抗菌剂发挥作用。公认的催化机制称为卤素循环，包括HO对LPO进行两电子氧化以产生氧合铁（IV）自由基，随后氧原子转移至SCN。然而，该机制无法解释双相动力学以及在还原底物浓度较低时HO的抑制作用，而这些情况可能具有生物学相关性。我们提出了一种有序序列机制，其中底物结合顺序相反，先是SCN，然后是HO。卤素循环机制所描述的底物结合顺序实际上具有抑制作用。
