Oxidation of ω-Oxo Fatty Acids by Cytochrome P450_BM-3(CYP102)

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• 作者：Davis ; S. Christopher ; Sui ; Zhihua ; Peterson ; Julian A. ; de Montellano ; Paul R. Ortiz
• 刊名：Archives of Biochemistry and Biophysics
• 出版年：1996
• 期刊代码：116_00039861
• 类别：ch
• 出版时间：April 1, 1996
• 卷：328
• 期：1
• 页码：35-42
• 文件大小：187 K

摘要

Cytochrome P450 enzymes oxidize aldehydes either to the corresponding acid or, via a decarboxylation mechanism, to an olefin one carbon shorter than the parent substrate. To explore the factors that control partitioning between these two pathways, we have examined the cytochrome P450_BM-3(CYP102)-catalyzed oxidation of fatty acids with a terminal aldehyde group. P450_BM-3oxidizes 18-oxooctadecanoic, 16-oxohexadecanoic, 14-oxotetradecanoic, and 12-oxododecanoic acids exclusively to the corresponding α,ω-diacids. The rates of these oxidations decrease in the order C₁₆> C₁₈g align=center border=0 SRC=/images/glyphs/BQ2.GIF> C₁₄> C₁₂. No kinetic isotope effect is observed nor is the catalytic outcome altered when the aldehyde hydrogen is replaced by a deuterium in 16-oxohexadecanoic acid. The only product observed with 16-oxohexadecanoic acid is the diacid even when a 13,14-double bond or 15-methyl groups, substitutions that should stabilize the proposed radical intermediate generated by decarboxylation, are present. The oxidation of 16-oxohexadecanoic acid is not supported by H₂O₂. The results demonstrate that aldehyde oxidation by cytochrome P450_BM-3is insensitive to changes in substrate structure expected to stabilize the transition state for decarboxylation. Decarboxylation, in contrast to the oxidation of aldehydes to acids, depends on specific substrate–protein interactions and is enzyme-specific.