Cytochrome P450 2A6 and other human P450 enzymes in the oxidation of flavone and flavanone.
Cytochrome P450 2A6 and other human P450 enzymes in the oxidation of flavone and flavanone.
复制标题
DOI：
10.1080/00498254.2018.1426133
复制
发表时间：
2019-03
期刊：
影响因子：
--
通讯作者：
Shimada T
中科院分区：
文献类型：
--
作者：
Kakimoto K;Murayama N;Takenaka S;Nagayoshi H;Lim YR;Kim V;Kim D;Yamazaki H;Komori M;Guengerich FP;Shimada T
1.我们以前报道过黄酮类和黄烷酮类化合物与细胞色素P450(P450或CYP)2A6和2A13等人P450酶相互作用，并抑制这些P450酶的催化活性。在本研究中，我们研究了CYP1A1、1A2、1B1、2A6、2A13、2C9和3A4氧化黄酮类和黄烷酮的能力。2.人P450s将黄酮氧化为6-和5-羟基黄酮，7个未鉴定的单羟基黄酮和5个二羟基黄酮。其中，CYP2A6活性最强，能生成6-羟基和5-羟基黄酮以及几个单羟基和双羟基化产物。3.该酶催化黄烷酮生成2‘-羟基黄烷酮和6-羟基黄烷酮的活性也很高，转化率分别为4.8min−1和1.3min−1。其他黄烷酮代谢物有4‘-、3’-和7-羟基黄烷酮、3个未鉴定的单羟基黄烷酮和5个单羟基黄酮酮，其中包括6-羟基黄酮酮。该酶催化黄烷酮的转化率为0.72min−1，是其转化率(0.29min−1)的3倍左右。4.这些结果表明，CYP2A6和其他人类P450在代谢膳食中存在的两种不可替代的黄酮类化合物--黄酮类和黄烷酮中起着重要的作用。讨论了P450催化黄酮脱饱和生成黄酮类化合物的化学机理。
1. We previously reported that flavone and flavanone interact spectrally with cytochrome P450 (P450 or CYP) 2A6 and 2A13 and other human P450s and inhibit catalytic activities of these P450 enzymes. In this study, we studied abilities of CYP1A1, 1A2, 1B1, 2A6, 2A13, 2C9, and 3A4 to oxidize flavone and flavanone. 2. Human P450s oxidized flavone to 6-and 5-hydroxylated flavones, seven uncharacterized mono-hydroxylated flavones, and five di-hydroxylated flavones. CYP2A6 was most active in forming 6-hydroxy-and 5-hydroxyflavones and several mono-and di-hydroxylated products. 3. CYP2A6 was also very active in catalyzing flavanone to form 2´-and 6-hydroxyflavanones, the major products, at turnover rates of 4.8 min−1 and 1.3 min−1, respectively. Other flavanone metabolites were 4´-, 3´-and 7-hydroxyflavanone, three uncharacterized mono-hydroxylated flavanones, and five mono-hydroxylated flavones, including 6-hydroxyflavone. CYP2A6 catalyzed flavanone to produce flavone at a turnover rate of 0.72 min−1 that was ~3-fold higher than that catalyzed by CYP2A13 (0.29 min−1). 4. These results indicate that CYP2A6 and other human P450s have important roles in metabolizing flavone and flavanone, two unsubstituted flavonoids, present in dietary foods. Chemical mechanisms of P450-catalyzed desaturation of flavanone to form flavone are discussed.
登录
查看更多内容
影响因子：
1.8
作者：
Kagawa, H;Takahashi, T;Harigaya, Y
通讯作者：
Harigaya, Y
影响因子：
4.3
作者：
Arnqvist, Lisa;Persson, Mattias;Sitbon, Folke
通讯作者：
Sitbon, Folke
影响因子：
2.9
作者：
BROWN, RE;JARVIS, KL;HYLAND, KJ
通讯作者：
HYLAND, KJ
影响因子：
7.4
作者：
Du, Yegang;Chu, Hung;Lo, Clive
通讯作者：
Lo, Clive
影响因子：
4.8
作者：
Johnson, Kevin M.;Phan, Thanh T. N.;Guengerich, F. Peter
通讯作者：
Guengerich, F. Peter