Ortiz de Montellano P R, Komives E A
J Biol Chem. 1985 Mar 25;260(6):3330-6.
Phenylacetylene and biphenylacetylene are oxidized by cytochrome P-450 to the corresponding arylacetic acids. The acetylenic hydrogen shifts to the adjacent carbon and one atom of molecular oxygen is incorporated into the carboxylic acid group in these transformations, which are subject to a large kinetic isotope effect when the acetylenic hydrogen is replaced by deuterium. The same products and isotope effects are observed when the two arylacetylenes are oxidized by m-chloroperbenzoic acid rather than by the enzyme. In contrast, the inactivation of cytochrome P-450 that occurs during the oxidation of phenylacetylene is insensitive to deuterium substitution. The partition ratio between metabolite formation and enzyme inactivation consequently changes from 26 to 15 in going from phenylacetylene to the deuterated analogue. Metabolite formation therefore diverges from heme alkylation very early in the catalytic process.
苯乙炔和联苯乙炔被细胞色素P - 450氧化为相应的芳基乙酸。炔氢转移至相邻碳原子，在这些转化过程中，一个分子氧原子并入羧酸基团，当炔氢被氘取代时，这些转化会受到很大的动力学同位素效应影响。当这两种芳基乙炔被间氯过苯甲酸而非酶氧化时，会观察到相同的产物和同位素效应。相比之下，苯乙炔氧化过程中发生的细胞色素P - 450失活对氘取代不敏感。因此，从苯乙炔到氘代类似物，代谢物形成与酶失活之间的分配比从26变为15。所以，在催化过程的早期，代谢物形成就与血红素烷基化产生了分歧。
