Odorant metabolism of the olfactory cleft mucus in idiopathic olfactory impairment patients and healthy volunteers

Abstract

Background: It remains unclear whether the metabolic activity of nasal mucus in the olfactory and respiratory areas is different. Moreover, age-and olfactionrelated changes may affect metabolism.Methods: Hexanal, octanal, and 2-methylbutanal were selected for in vitro metabolism analysis and compared between the olfactory cleft and respiratory mucus of participants < 50-year-old with normal olfaction using gas chromatography mass spectrometry. The metabolic activity of hexanal in the olfactory cleft mucus was further compared between three groups, (1) normal olfaction, age < 50 years old, (2) normal olfaction, age ≥50 years old, and (3) idiopathic olfactory impairment. To characterize the enzyme(s) responsible for aldehyde reduction, we also tested if epalr22897estat and 3,5-dichlorosalicylic acid, types of reductase inhibitors, affect metabolism.Results: Conversion of aldehydes to their corresponding alcohols was observed in the olfactory cleft and respiratory mucus. The metabolic production of hexanol, octanol, and 2-methybutanol was significantly higher in the olfactory cleft mucus than in the respiratory mucus (p < 0.01). The metabolic conversion of hexanal to hexanol in the mucus of the idiopathic olfactory impairment group was significantly lower than that in the age-matched normal olfaction group. Excluding the nicotinamide adenine dinucleotide phosphate (NADPH) regenerating system from the reaction mixture inhibited metabolism. The addition of either epalr22897estat or 3,5-dichlorosalicylic acid did not inhibit this metabolic conversion. Conclusions:The enzymatic metabolism of odorants in the olfactory cleft mucus is markedly higher than in the respiratory mucus and decreases in patients with idiopathic olfactory impairment.

Odorant Metabolism in Humans

“…More recently, the same group investigated the conversion of aldehydes to their corresponding alcohols in the human mucus obtained from the olfactory cleft or respiratory tissue, the latter showing a lower metabolism for octanal, hexanal, and 2‐methybutanal. Additionally, hexanal mucus metabolism was significantly lower in participants with idiopathic olfactory impairment [66] . Takaoka et al.…”

“…Additionally, hexanal mucus metabolism was significantly lower in participants with idiopathic olfactory impairment. [66] Takaoka et al showed the enzymatically driven oxidation of aldehydes to their corresponding carboxylic acid, and the involvement of aldehyde oxidases in mouse. Since AOX are also found in in the human OE this might give a starting point for further investigations.…”

“…Hexanal metabolism showed a significantly lower metabolism in the mucus of patients with idiopathic impairment. Disease and injury conditions as well as influences by respective medication are thus further factors which deserve to be considered when studying individual differences in odorant metabolism [66] . In a recent study it was shown that patients undergoing chemotherapy and having smell impairment had bigger problems with food intake than patients without olfactory impairment [118] .…”

Geruchsstoffmetabolismus im Menschen

“…(2022) [66] zeigten kürzlich, dass die Geruchsstoffe Hexanal, Octanal und 2‐Methylbutanal in In‐vitro ‐ Experimenten durch menschlichen Mukus verstoffwechselt werden. Der Hexanal‐Stoffwechsel war hierbei bei Versuchspersonen mit idiopathischer Beeinträchtigung deutlich geringer [66] . Krankheits‐ und Verletzungszustände sowie Einflüsse durch entsprechende Medikamente sind daher weitere Faktoren, die bei der Untersuchung individueller Unterschiede im Geruchsstoffmetabolismus berücksichtigt werden sollten [66] .…”

“…Ein weiterer Aspekt betrifft die Entwicklung von Diagnoseinstrumenten: Das Verständnis des Geruchsstoffmetabolismus bei gesunden und erkrankten Personen könnte zur Entwicklung nicht-invasiver Screening-Methoden für eine Vielzahl von Krankheiten beitragen. Prominente Marker wie Aceton bei Diabetes [116] konnten als Indikatoren für andere Krankheiten wie Krebs oder Parkinson [117] [66] zeigten kürzlich, dass die Geruchsstoffe Hexanal, Octanal und 2-Methylbutanal in Invitro-Experimenten durch menschlichen Mukus verstoffwechselt werden. Der Hexanal-Stoffwechsel war hierbei bei Versuchspersonen mit idiopathischer Beeinträchtigung deutlich geringer.…”