Characterization of human oxidoreductases involved in aldehyde odorant metabolism

Abstract

Oxidoreductases are major enzymes of xenobiotic metabolism. Consequently, they are essential in the chemoprotection of the human body. Many xenobiotic metabolism enzymes have been shown to be involved in chemosensory tissue protection. Among them, some were additionally shown to be involved in chemosensory perception, acting in signal termination as well as in the generation of metabolites that change the activation pattern of chemosensory receptors. Oxidoreductases, especially aldehyde dehydrogenases and aldo–keto reductases, are the first barrier against aldehyde compounds, which include numerous odorants. Using a mass spectrometry approach, we characterized the most highly expressed members of these families in the human nasal mucus sampled in the olfactory vicinity. Their expression was also demonstrated using immunohistochemistry in human epitheliums sampled in the olfactory vicinity. Recombinant enzymes corresponding to three highly expressed human oxidoreductases (ALDH1A1, ALDH3A1, AKR1B10) were used to demonstrate the high enzymatic activity of these enzymes toward aldehyde odorants. The structure‒function relationship set based on the enzymatic parameters characterization of a series of aldehyde odorant compounds was supported by the X-ray structure resolution of human ALDH3A1 in complex with octanal.

Characterization of a Human Respiratory Mucosa Model to Study Odorant Metabolism

“…While some proteomic analyses did not detect DCXR, 40 others were sensitive enough to verify the protein in the human nasal mucus. 14 DCXR protein has been previously found in the human respiratory mucosa, 5 which is in line with what we observed in the present study. According to the human protein atlas, 41 DCXR has also been detected in low amounts in fibroblasts, which could explain the punctual staining observed in the fibroblast-loaded connective tissue.…”

“…Concerning ALDH1A1, its expression in the human nasal turbinate and olfactory cleft has been previously shown by our team. 14 We demonstrated that this enzyme is strongly expressed in the epithelial layer. As ADLH1A1 is a secreted enzyme, we suggested that nasal glands might be involved in this process.…”

“…As ADLH1A1 is a secreted enzyme, we suggested that nasal glands might be involved in this process. 14 For ALDH3A1, relatively low gene expression correlated with strong immunofluorescent signals in the tissue model epithelial layer. Since data on gene expression and protein abundance do not always correlate, XME localization in tissues and functionality should be explored.…”

“…ALDH1A1 and ALDH3A1 have been recently proven to be relevant for human chemical senses. 14,20 In our previous study, we found these isoforms in the human olfactory tissue vicinity and in human saliva, and these isoforms were able to metabolize a range of aldehyde flavoring agents such as benzaldehyde. 14 We previously verified DCXR, ALDH1A1, and ALDH3A1 in ex vivo samples of human nasal mucus and tissue specimens of the olfactory vicinity.…”

The coming future: The role of the oral–microbiota–brain axis in aroma release and perception

“…Human aldehyde dehydrogenases have recently been discovered to metabolize odorant aldehydes. Additionally, in the same study, these enzymes were shown to be highly expressed in the oral cavity (Boichot et al., 2023).…”