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. Significance StatementCarbohydrates strongly motivate eating, yet most are consumed in complex forms that do not immediately release glucose. We show that the oral epithelium contains an adaptive enzymatic-metabolic sensing system that enables rapid evaluation of glucose-yielding carbohydrates before digestion. Two enzymes, maltase glucoamylase and glucokinase, act locally in taste fields to preprocess and metabolically assess complex sugars, biasing ingestive behavior toward energetically favorable foods. This mechanism operates independently of canonical sweet taste receptors and is dynamically regulated by dietary experience and receptor sensitivity. These findings reveal that the mouth actively estimates the energetic value of food prior to ingestion, reshaping our understanding of how nutrient sensing guides dietary choice.