7-HETE, 1O-HETE, AND 13-HETE ARE MAJOR PRODUCTS OF NADPH-DEPENDENT ARACHIDONIC-ACID METABOLISM IN RAT-LIVER MICROSOMES - ANALYSIS OF THEIR STEREOCHEMISTRY, AND THE STEREOCHEMISTRY OF THEIR ACID-CATALYZED REARRANGEMENT
7-HETE, 1O-HETE, AND 13-HETE ARE MAJOR PRODUCTS OF NADPH-DEPENDENT ARACHIDONIC-ACID METABOLISM IN RAT-LIVER MICROSOMES - ANALYSIS OF THEIR STEREOCHEMISTRY, AND THE STEREOCHEMISTRY OF THEIR ACID-CATALYZED REARRANGEMENT
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DOI：
10.1006/abbi.1995.1421
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发表时间：
1995-08-20
影响因子：
3.9
通讯作者：
BLAIR, IA
中科院分区：
文献类型：
--
作者：
BRASH, AR;BOEGLIN, WE;BLAIR, IA
在苯巴比妥治疗的大鼠肝微粒体的NADPH依赖反应中，形成了[C-14]花生四烯酸代谢产物的复杂轮廓。这些产物通过高效液相色谱进行解析，并最初使用在线二极管阵列检测器进行分析，该检测器设置为监测205、220、235和270 nm。除了环氧二十碳三烯酸及其二醇水解产物外，主要的羟基二十碳四烯酸(HETE)代谢物还被鉴定为欧米伽-羟基衍生物和三种双烯丙基产物，即7-HETE、10-HETE和13-HETE。Oliw ct al报道了13-HETE的形成。(拱门。生物化学。生物群落。300、434-439(1993))。新产物的结构经GC-MS确证，10-HETE的结构通过与正品合成材料的比较而确定。手性柱分析表明，7-HETE和10-HETE基本上是外消旋的。13-HETE以40：60的比例分解为13S：13R。在弱酸性条件下(1%的醋酸)，双烯丙基HETE很容易重排成含有HETE的共轭二烯。使用[(18)]13-HETE，我们观察到标记氧在11-和1B-HETE重排产物中的保留率为69%。此外，对酸处理的10-HETE和13-HETE对映体的立体分析表明，在温和的酸催化重排过程中，手性部分保留(甲酯对映体的比例为80：20，游离酸的比例为60：40)。这代表了这类细胞色素P450的花生四烯酸代谢物的一种新反应。(C)1995年学术出版社。
A complex profile of metabolites of [C-14]arachidonic acid are formed in NADPH-dependent reactions in liver microsomes from phenobarbital-treated rats. The products were resolved by HPLC and analyzed initially with an on-line diode array detector set to monitor 205, 220, 235, and 270 nm. In addition to the epoxyeicosatrienoic acids and their diol hydrolysis products, prominent hydroxyeicosatetraenoic acids (HETE) metabolites were identified as omega-hydroxy derivatives and three bis-allylic products, 7-HETE, 10-HETE, and 13-HETE. The formation of 13-HETE was reported by Oliw ct al. (Arch. Biochem. Biophys. 300, 434-439 (1993)). Structures of the new products were established by GC MS, and for 10-HETE, by comparison to authentic synthetic material. Chiral column analysis indicated that 7-HETE and 10-HETE were essentially racemic. The 13-HETE resolved into a 40:60 ratio of 13S:13R. The bis-allylic HETEs readily undergo rearrangement to conjugated diene containing HETEs in mild acidic conditions (1% acetic acid). Using [(18)]13-HETE we observed 69% retention of the labeled oxygen in the 11- and 1B-HETE rearrangement products. Furthermore, steric analysis of products from acid treated 10-HETE and 13-HETE enantiomers revealed partial retention of chirality (80:20 ratio of enantiomers for methyl esters, and 60:40 ratio for free acids) in the course of mild acid-catalyzed rearrangement. This represents a novel reaction of this class of arachidonic acid metabolites of cytochromes P450. (C) 1995 Academic Press, Inc.