“…Groups were made with UniProt classification according to previous publications, which demonstrated either a role in the detoxification of toxic compounds such as the aldo–keto reductase family 1 member A1 (AKR1A1) 31 , 32 , a role in the antioxidant capacity by trapping or destroying free radicals such as superoxide dismutase 33 , or both, such as glutathione transferase Mu 2 34 – 36 . Additionally, enzymes and proteins already shown to be involved in human olfaction were identified in this proteome, including glutathione transferases, GSTP1 20 , 37 , 38 and l -xylulose reductase (DCXR) 16 , and lipocalins, LCN1 39 , LCN2 39 , and OBPIIa 14 , 40 , also known as odorant binding proteins, as they can bind odorants (Supplemental Table 6 ). Figure 1 Classification of human nasal mucus proteins.…”
Section: Resultsmentioning
confidence: 99%
“…In this study, we observed high expression of xenobiotic metabolism enzymes in the human nasal mucus sampled in the olfactory cleft of three different people. Some enzymes identified in these proteomes as GSTs or DCXR were previously shown to be involved in human odor perception 16 , 20 , 37 , 38 . Additionally, new enzymes, potentially involved in odorant metabolization appear as interesting targets for further studies as the sulfotransferase (SULT1A1).…”
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.
“…Groups were made with UniProt classification according to previous publications, which demonstrated either a role in the detoxification of toxic compounds such as the aldo–keto reductase family 1 member A1 (AKR1A1) 31 , 32 , a role in the antioxidant capacity by trapping or destroying free radicals such as superoxide dismutase 33 , or both, such as glutathione transferase Mu 2 34 – 36 . Additionally, enzymes and proteins already shown to be involved in human olfaction were identified in this proteome, including glutathione transferases, GSTP1 20 , 37 , 38 and l -xylulose reductase (DCXR) 16 , and lipocalins, LCN1 39 , LCN2 39 , and OBPIIa 14 , 40 , also known as odorant binding proteins, as they can bind odorants (Supplemental Table 6 ). Figure 1 Classification of human nasal mucus proteins.…”
Section: Resultsmentioning
confidence: 99%
“…In this study, we observed high expression of xenobiotic metabolism enzymes in the human nasal mucus sampled in the olfactory cleft of three different people. Some enzymes identified in these proteomes as GSTs or DCXR were previously shown to be involved in human odor perception 16 , 20 , 37 , 38 . Additionally, new enzymes, potentially involved in odorant metabolization appear as interesting targets for further studies as the sulfotransferase (SULT1A1).…”
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.
“…To measure the ability of AmGSTD1 to interact with odorant molecules, we used a previously published method [35,43,44]. The CDNB enzyme-based competition assay allows us to identify compounds that are conjugated or bind the enzyme without conjugation (ligandin function) to decrease enzymatic activity towards CDNB.…”
Glutathione transferases (GST) are detoxification enzymes that conjugate glutathione to a wide array of molecules. In the honey bee Apis mellifera, AmGSTD1 is the sole member of the delta class of GSTs, with expression in antennae. Here, we structurally and biochemically characterized AmGSTD1 to elucidate its function. We showed that AmGSTD1 can efficiently catalyse the glutathione conjugation of classical GST substrates. Additionally, AmGSTD1 exhibits binding properties with a range of odorant compounds. AmGSTD1 has a peculiar interface with a structural motif we propose to call ‘sulfur sandwich’. This motif consists of a cysteine disulfide bridge sandwiched between the sulfur atoms of two methionine residues and is stabilized by CH…S hydrogen bonds and S…S sigma‐hole interactions. Thermal stability studies confirmed that this motif is important for AmGSTD1 stability and, thus, could facilitate its functions in olfaction.
“…Some enzymes able to metabolize odorants are also involved in tastant metabolism. Indeed, a recent study revealed the ability of two salivary glutathione transferase isoforms (GSTA1 and GSTP1) to metabolize bitter compounds such as isothiocyanates (Schwartz et al, 2022). Interestingly, the salivary enzymatic content can be modulated by the diet.…”
Section: Cystatins and Histatinsmentioning
confidence: 99%
“…Structurally unrelated cysteine-modifying agents, such as cinnamaldehyde, isothiocyanates or allicin, activate TRPA1 via covalent modification of cysteine residues (Hinman et al, 2006;Macpherson et al, 2007). Some of these compounds, in particular isothiocyanates, are metabolized by GSTs (Schwartz et al, 2022), suggesting a possible impact on the activation of TRPA1. Moreover, activation of mechanoreceptors depends on the lubrification of the oral cavity, which depends on saliva and its composition (Bongaerts et al, 2007;Yakubov et al, 2015).…”
Section: Trigeminal Compounds and Salivary Proteinsmentioning
The sensory perception of food is a complex phenomenon involving the integration of different stimuli (aroma, taste, trigeminal sensations, texture and visual). Flavor compounds activate odorant, taste and trigeminal chemoreceptors, generating a depolarization of the sensory neurons and then the consciousness of food flavor perception. Recent studies are increasingly highlighting the importance of perireceptor events, which include all the molecular events surrounding the receptors, in the modulation of flavor perception. These events affect the quantity and quality of flavor compounds in the environment of chemoreceptors. They include the metabolization of flavor compounds by enzymes present in biological fluids (saliva and mucus) and the oronasal epithelia and noncovalent interactions with binding proteins. Perireceptor mechanisms have been extensively studied in insects and mammals, demonstrating the importance of the entailed processes in the termination of the chemical signal. In humans, research is in full swing. Here, we reviewed the perireceptor mechanisms recently reported in vitro, in biological fluids and in cells and in vivo in humans. These studies indicate that perireceptor mechanisms likely have an important contribution to flavor perception. This mini-review focuses on recent pioneering studies that are paving the way for this new research area. It also suggests that new approaches taking into account the real conditions of food consumption will be required in the future to accurately address this question.
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