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克隆、纯化和鉴定非人灵长类 12/15-脂氧合酶。

Cloning, purification and characterization of non-human primate 12/15-lipoxygenases.

机构信息

Orexo AB, P.O. Box 303, 751 05 Uppsala, Stockholm, Sweden.

出版信息

Prostaglandins Leukot Essent Fatty Acids. 2010 Feb-Mar;82(2-3):121-9. doi: 10.1016/j.plefa.2009.11.006. Epub 2010 Jan 27.

DOI:10.1016/j.plefa.2009.11.006
PMID:20106647
Abstract

The enzyme 15-lipoxygenase-1 (15-LO-1) possesses mainly 15-LO activity and has so far only been described in human cells and rabbit reticulocytes. The animal ortholog, except rabbit reticulocytes, is an enzyme with predominantly a 12-lipoxygenase activity, commonly referred to as 12/15-LO. We describe herein the characterization of the 12/15-LOs in Macaca mulatta (rhesus monkey) and in Pongo pygmaeus (orang-utan). The rhesus and the orang-utan enzymes have mainly 12-lipoxygenase and 15-lipoxygenase activity, respectively, and they display 94% and 98% identity to the human 15-LO-1 protein. The rhesus enzyme was functionally different from the human enzyme with respect to substrate utilization in that anandamide was used differently and that the rhesus enzymes positional specificity could be affected by the substrate concentration. Furthermore, genomic data indicate that chimpanzees express an enzyme with mainly 15-lipoxygenase activity whereas marmosets express an enzyme with mainly 12-LO activity. Taken together, the switch during evolution from a 12-lipoxygenating enzyme in lower primates to a 15-lipoxygenating enzyme in higher primates and man might be of importance for the biological function of this enzyme.

摘要

15-脂氧合酶-1(15-LO-1)主要具有 15-LO 活性,迄今为止仅在人类细胞和兔网织红细胞中描述过。动物同源物(除兔网织红细胞外)是一种主要具有 12-脂氧合酶活性的酶,通常称为 12/15-LO。本文描述了猕猴(恒河猴)和猩猩(猩猩)中 12/15-LO 的特征。恒河猴和猩猩的酶主要具有 12-脂氧合酶和 15-脂氧合酶活性,分别与人 15-LO-1 蛋白具有 94%和 98%的同一性。恒河猴酶在底物利用方面与人类酶具有不同的功能,因为大麻素的利用方式不同,并且恒河猴酶的位置特异性可能受到底物浓度的影响。此外,基因组数据表明,黑猩猩表达一种主要具有 15-脂氧合酶活性的酶,而狨猴表达一种主要具有 12-LO 活性的酶。总之,在进化过程中,从低级灵长类动物的 12-脂氧合酶到高级灵长类动物和人类的 15-脂氧合酶的转变可能对这种酶的生物学功能很重要。

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