James M O, Boyle S M
Department of Medicinal Chemistry, College of Pharmacy and the Whitney Marine Laboratory, University of Florida, Gainesville 32610-0485, USA.
Comp Biochem Physiol C Pharmacol Toxicol Endocrinol. 1998 Nov;121(1-3):157-72. doi: 10.1016/s0742-8413(98)10036-1.
Since the last review of this topic, further insight has been gained into the presence and functions of cytochrome P450 proteins in the hepatopancreas and other organs of aquatic crustacean species, although progress has been slow relative to the advances in other species. Recent studies with several lobster, shrimp, crab and crayfish species suggest that cytochromes P450 in the 2 and 3 families are the most abundant forms in hepatopancreas microsomes. Substrates normally metabolized by CYP2 and CYP3 family members are monooxygenated more rapidly by crustacea than substrates normally metabolized by CYP1 family enzymes, e.g. erythromycin, testosterone and aminopyrine are much more rapidly monooxygenated than ethoxyresorufin. Some progress has been made in cloning and sequencing crustacean P450 forms. CYP2L1 and CYP2L2 cDNA sequences have been cloned from spiny lobster hepatopancreas libraries, and there was evidence for at least two more cytochromes P450 in spiny lobster hepatopancreas. An area of continued interest, but of no consensus or general findings, relates to the presence and inducibility of CYP1 family members in crustacea. Some studies indicate weak induction of total cytochrome P450 and increased turnover of substrates normally associated with CYP1, while others show no effect of the classic inducers that act at the Ah receptor in vertebrates. A few studies of the roles of cytochromes P450 in the biosynthesis and degradation of steroids, including ecdysteroids, have been published. Further studies are needed to understand the regulation and normal function of the crustacean cytochromes P450.
自从上次对该主题进行综述以来,人们对细胞色素P450蛋白在水生甲壳类动物的肝胰腺和其他器官中的存在及功能有了更深入的了解,尽管相对于其他物种的进展而言,这一过程较为缓慢。最近对几种龙虾、虾、蟹和小龙虾物种的研究表明,2族和3族细胞色素P450是肝胰腺微粒体中最丰富的形式。通常由CYP2和CYP3家族成员代谢的底物在甲壳类动物中被单加氧的速度比通常由CYP1家族酶代谢的底物更快,例如,红霉素、睾酮和氨基比林被单加氧的速度比乙氧基亚砜红快得多。在克隆和测序甲壳类动物P450形式方面已经取得了一些进展。已从多刺龙虾肝胰腺文库中克隆出CYP2L1和CYP2L2 cDNA序列,并且有证据表明多刺龙虾肝胰腺中至少还有另外两种细胞色素P450。一个持续受到关注但尚无共识或普遍研究结果的领域涉及甲壳类动物中CYP1家族成员的存在及可诱导性。一些研究表明总细胞色素P450有微弱诱导,且通常与CYP1相关的底物周转增加,而其他研究则表明在脊椎动物中作用于芳烃受体的经典诱导剂没有影响。已经发表了一些关于细胞色素P450在类固醇(包括蜕皮类固醇)生物合成和降解中的作用的研究。需要进一步研究以了解甲壳类动物细胞色素P450的调节和正常功能。