Oxidation and rearrangements of flavanones by mammalian cytochrome P450
Oxidation and rearrangements of flavanones by mammalian cytochrome P450
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DOI：
10.1080/00498250400005708
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发表时间：
2004-09-01
期刊：
影响因子：
1.8
通讯作者：
Harigaya, Y
中科院分区：
文献类型：
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作者：
Kagawa, H;Takahashi, T;Harigaya, Y
1.为了阐明黄烷酮在哺乳动物体内的代谢途径，本研究考察了（+/-）-黄烷酮和（+/-）-4 '-甲氧基黄烷酮在大鼠肝微粒体和重组人P450中的代谢，其中P450的结构变化是容易识别的.在大鼠肝微粒体中，黄酮和（+/-）-2，3-反式二氢黄酮醇以及4 '-甲氧基黄酮和（+/-）-2，3-反式-4'-甲氧基二氢黄酮醇的形成依赖于NADPH的β-烟酰胺腺嘌呤二核苷酸磷酸（NADPH）.重组人P450除了从（+/-）-黄烷酮形成β-羟色胺外，还产生了相同的代谢物。用氘代（+/-）-黄烷酮和（+/-）-4 '-甲氧基黄烷酮考察了这些反应中的动力学同位素效应。在黄烷醇类化合物的生成过程中存在较强的同位素效应，而在黄酮类化合物的生成过程中同位素效应较小。结果表明，P450介导的（+/-）-黄烷酮和（+/-）-4 '-甲氧基黄烷酮向相应代谢物的转化是通过从黄烷酮的C-2-或C-3-位上夺取氢自由基进行的.通过测定黄嘌呤-黄嘌呤氧化酶-细胞色素c体系中的超氧化物清除活性，研究了黄烷酮及其代谢产物的抗氧化特性。（+/-）-2，3-trans-Flavanonol的活性高于其它黄酮类化合物.黄烷酮是由哺乳动物P450代谢，提供了重要的信息有关的代谢和药理作用的饮食黄烷酮。
1. To clarify the metabolic pathways of flavanones in mammals, the metabolism of (+/-)-flavanone and (+/-)-4'-methoxy flavanone by rat liver microsomes and recombinant human P450s in which structural changes are readily identifiable were examined.2. The beta-nicotinamide adenine dinucleotide phosphate (NADPH)-dependent formation of flavone plus (+/-)-2,3-trans-flavanonol and of 4'-methoxy flavone plus (+/-)-2,3-trans-4'-methoxy flavanonol, respectively, by rat liver microsomes was observed.3. The same metabolites were generated by recombinant human P450s in addition to the formation of isoflavone from (+/-)-flavanone.4. The kinetic isotope effects in these reactions were examined using deuterated (+/-)-flavanone and (+/-)-4'-methoxy flavanone. There was a strong isotope effect in the production of flavanonols, but the isotope effect in the production of flavones was small. The results indicated that the P450-mediated conversion of (+/-)-flavanone and of (+/-)-4'-methoxyflavanone to the corresponding metabolites proceeded via abstraction of a hydrogen radical from the C-2- or C-3-position of the flavanone skeleton.5. The antioxidant properties of flavanone and its metabolites were examined by measuring superoxide-scavenging activity in a xanthine-xanthine oxidase-cytochrome c system. (+/-)-2,3-trans-Flavanonol had higher activity than that of other flavonoids.6. Flavanones are metabolized by mammalian P450s, providing important information relevant to the metabolism and pharmacological action of dietary flavanones.