Nasal odorant metabolites: characterization and function in olfactory perception

功能性嗅觉对于评估和享受食物、接收有关同种物质的信息以及通过空气传播的化学线索检测威胁至关重要。嗅觉障碍与生活质量受损有关，反映在抑郁和社交不安全感等不良心理状态的发生率更高。此外，在世界范围内，老年人口不断增长，他们的嗅觉敏锐度随着年龄的增长而下降。解决和克服相关的嗅觉障碍问题需要对与嗅觉有关的外周和中枢过程有详细的了解。确实，有越来越多的研究揭示了塑造嗅觉的分子和细胞相互作用。NAOMI联盟成员最近的研究表明，进入生物体的气味可以通过代谢酶生物转化为本身具有信号特性的代谢物。此外，我们已经证明鼻部新陈代谢过程非常快(毫秒范围)，这意味着气味代谢物确实对嗅觉有重大影响。对这一迄今被忽视的机制的高级表征可能会从根本上改变我们对嗅觉检测的理解。到目前为止，涉及鼻气味生物转化的潜在酶过程从未被系统地研究过，而且对鼻挥发性代谢物的气味特征的了解非常有限。通过结合我们的专业知识，我们将通过动物和细胞模型以及在人类身上探索挥发性气味代谢物的形成、鉴定和感官特性，目的是全面了解鼻部代谢产品如何塑造香气和气味感知。

A functional sense of smell is essential for evaluating and enjoying food, receiving information about conspecifics, and detecting threats via airborne chemical cues. Olfactory dysfunction has been associated with an impaired quality of life, reflected by a higher incidence of undesirable mental states such as depression and social insecurity. Further, worldwide there is a growing elderly population, which experience declining olfactory acuity with age. Addressing and overcoming related olfactory dysfunction issues require a detailed understanding of peripheral and central processes implicated in olfaction. There is indeed a growing body of research unravelling molecular and cellular interactions that shape olfactory sensation. Recent studies from members of the NAOMI consortium have demonstrated that odorants entering the organism are biotransformed by metabolizing enzymes into metabolites that themselves have signaling properties. In addition, we have shown that nasal metabolism processes are very fast (millisecond range), meaning that odorous metabolites indeed have a significant impact on olfactory perception. An advanced characterization of this hitherto neglected mechanism could radically change our understanding of olfactory detection.The underlying enzymatic processes involved in nasal odorant biotransformation have never been investigated systematically, to date, and knowledge on the odor characteristics of nasal volatile metabolites is very limited. By combining our expertise, we will explore the formation, the identity and the sensory properties of volatile odorant metabolites via animal and cellular models and in man, with the aim of gaining a comprehensive understanding of how aroma and odor perception is shaped by nasal metabolic products.