An enzymatic-metabolic sensing axis in taste cells detects glucose-yielding carbohydrates.

Glucose is a potent reinforcer of intake, yet most foods contain complex saccharides that do not yield free glucose until after digestion. How the oral sensory system rapidly evaluates the potential metabolic value of food remains unclear. Here, we identify an oral enzymatic-metabolic sensing mechanism that enables detection of glucose-yielding carbohydrates independent of canonical sweet taste receptors. Using genetic, virogenetic, molecular, and behavioral approaches in mice, we show that glucokinase (GCK) in taste cells is necessary for the attraction to glucose-containing sugars. We further demonstrate that maltase glucoamylase (MGAM), a glycosidic enzyme expressed on and near taste cells, facilitates rapid oral sugar sensing. Disruption of either GCK or MGAM in the major taste fields selectively attenuates the attraction to maltose and a carbohydrate-rich mixed diet, establishing both as intermediaries in the initial transduction pathway for complex saccharides that ultimately give rise to nutrient reward. Molecular profiling of taste papillae further revealed that deficient sweet sensing was accompanied by a compensatory increase in lingual MGAM, highlighting an adaptive mechanism for maintaining oral carbohydrate sensitivity. Together, these findings reveal that the oral epithelium actively preprocesses and metabolically evaluates dietary carbohydrates, providing a mechanism for rapid estimation of energetic value prior to ingestion.