Enzymology of vertebrate carotenoid oxygenases.
Enzymology of vertebrate carotenoid oxygenases.
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DOI：
10.1016/j.bbalip.2020.158653
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发表时间：
2020-11
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--
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中科院分区：
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哺乳动物和包括人类在内的高等脊椎动物只有类胡萝卜素裂解双加氧酶家族的三个成员。本综述重点关注具有类胡萝卜素加氧酶功能的两种酶。 β-胡萝卜素 15,15'-双加氧酶 (BCO1) 通过添加分子氧来催化 β-胡萝卜素键中心 15,15' 碳-碳双键的氧化裂解。反应产物是视黄醛（视黄醛或β-apo-15-胡萝卜醛）。因此，BCO1 是负责将维生素原 A 类胡萝卜素转化为维生素 A 的酶。它还能裂解 β-脱胡萝卜素的 15,15' 键以产生视黄醛，并裂解番茄红素以产生 apo-15-番茄红素。 β-胡萝卜素 9',10'-双加氧酶 (BCO2) 可催化多种类胡萝卜素的 9,10 和 9',10' 双键裂解，包括维生素原 A 和非维生素原 A 类胡萝卜素，以及叶黄素、叶黄素和玉米黄质。事实上，该酶显示出对利用这些叶黄素和其他具有羟基化末端环的底物的明显偏好。对 BCO1 缺失、BCO2 缺失和 BCO1/2 双敲除小鼠以及酶多态性人类的表型研究阐明了这些酶在全身类胡萝卜素和维生素 A 稳态中的作用。这些研究还证明了酶表达与全身脂质和能量代谢以及氧化应激之间的关系。此外，还观察到BCO1和BCO2与代谢疾病、眼病和癌症的发生或风险之间的关系。虽然酶在大多数疾病的病理生理学中的确切作用目前尚不清楚，但这些知识空白为未来严格的研究提供了肥沃的土壤。
Mammals and higher vertebrates including humans have only three members of the carotenoid cleavage dioxygenase family of enzymes. This review focuses on the two that function as carotenoid oxygenases. β-Carotene 15,15’-dioxygenase (BCO1) catalyzes the oxidative cleavage of the central 15,15’ carbon-carbon double of β-carotene bond by addition of molecular oxygen. The product of the reaction is retinaldehyde (retinal or β-apo-15-carotenal). Thus, BCO1 is the enzyme responsible for the conversion of provitamin A carotenoids to vitamin A. It also cleaves the 15,15’ bond of β-apocarotenals to yield retinal and of lycopene to yield apo-15-lycopenal. β-Carotene 9’,10’-dioxygenase (BCO2) catalyzes the cleavage of the 9,10 and 9’,10’ double bonds of a wider variety of carotenoids, including both provitamin A and non-provitamin A carotenoids, as well as the xanthophylls, lutein and zeaxanthin. Indeed, the enzyme shows a marked preference for utilization of these xanthophylls and other substrates with hydroxylated terminal rings. Studies of the phenotypes of BCO1 null, BCO2 null, and BCO1/2 double knockout mice and of humans with polymorphisms in the enzymes, has clarified the role of these enzymes in whole body carotenoid and vitamin A homeostasis. These studies also demonstrate the relationship between enzyme expression and whole body lipid and energy metabolism and oxidative stress. In addition, relationships between BCO1 and BCO2 and the development or risk of metabolic diseases, eye diseases and cancer have been observed. While the precise roles of the enzymes in the pathophysiology of most of these diseases is not presently clear, these gaps in knowledge provide fertile ground for rigorous future investigations.
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