Lobo Glenn P, Amengual Jaume, Palczewski Grzegorz, Babino Darwin, von Lintig Johannes
Case Western Reserve University, School of Medicine, Department of Pharmacology, Cleveland, OH 44106, USA.
Biochim Biophys Acta. 2012 Jan;1821(1):78-87. doi: 10.1016/j.bbalip.2011.04.010. Epub 2011 May 4.
Humans depend on a dietary intake of lipids to maintain optimal health. Among various classes of dietary lipids, the physiological importance of carotenoids is still controversially discussed. On one hand, it is well established that carotenoids, such as β,β-carotene, are a major source for vitamin A that plays critical roles for vision and many aspects of cell physiology. On the other hand, large clinical trials have failed to show clear health benefits of carotenoids supplementation and even suggest adverse health effects in individuals at risk of disease. In recent years, key molecular players for carotenoid metabolism have been identified, including an evolutionarily well conserved family of carotenoid-oxygenases. Studies in knockout mouse models for these enzymes revealed that carotenoid metabolism is a highly regulated process and that this regulation already takes place at the level of intestinal absorption. These studies also provided evidence that β,β-carotene conversion can influence retinoid-dependent processes in the mouse embryo and in adult tissues. Moreover, these analyses provide an explanation for adverse health effects of carotenoids by showing that a pathological accumulation of these compounds can induce oxidative stress in mitochondria and cell signaling pathways related to disease. Advancing knowledge about carotenoid metabolism will contribute to a better understanding of the biochemical and physiological roles of these important micronutrients in health and disease. This article is part of a Special Issue entitled Retinoid and Lipid Metabolism.
人类依靠膳食中摄入脂质来维持最佳健康状态。在各类膳食脂质中，类胡萝卜素的生理重要性仍存在争议。一方面，众所周知，类胡萝卜素，如β,β - 胡萝卜素，是维生素A的主要来源，而维生素A在视觉和细胞生理学的许多方面都起着关键作用。另一方面，大型临床试验未能显示补充类胡萝卜素对健康有明显益处，甚至表明对有疾病风险的个体可能有不良健康影响。近年来，已确定了类胡萝卜素代谢的关键分子参与者，包括一个进化上高度保守的类胡萝卜素加氧酶家族。对这些酶的基因敲除小鼠模型的研究表明，类胡萝卜素代谢是一个高度受调控的过程，而且这种调控在肠道吸收水平就已发生。这些研究还证明，β,β - 胡萝卜素的转化可影响小鼠胚胎和成年组织中依赖视黄酸的过程。此外，这些分析通过表明这些化合物的病理性积累可诱导线粒体中的氧化应激以及与疾病相关的细胞信号通路，从而为类胡萝卜素的不良健康影响提供了解释。增进对类胡萝卜素代谢的了解将有助于更好地理解这些重要微量营养素在健康和疾病中的生化及生理作用。本文是名为“视黄酸和脂质代谢”的特刊的一部分。
