A Biochemistry Question-Guided Derivation of a Potential Mechanism for HbA1c Formation in Diabetes Mellitus Leading to a Data-Driven Clinical Diagnosis

Abstract

A unique homework exercise with a related clinical case study has been designed as a tool for teaching applied biochemistry. Within the framework of the homework exercise, students derive a mechanism for the covalent attachment of glucose to hemoglobin. This process is critical to understand both nonenzymatic glycation and the molecular basis of diabetes mellitus. The homework exercise teaches first-principles using a data-driven, question-guided approach. The accompanying case study contextualizes the principles derived by students into a tangible clinical application. In the case study, students interpret analytical chemistry data from a clinical setting for a diabetic patient and must make conclusions on the best control and treatment for the patient. To make the proper clinical assessment, students must understand the mechanistic principles regarding nonenzymatic glycation of proteins that they learned in the homework exercise. Overall, the homework exercise and the case study tether together principles from organic chemistry (electrophiles/nucleophiles, Brønsted–Lowry acid–base theory, thermodynamics, blood glucose concentration, and cation exchange column chromatography) with those from biochemistry (covalent and noncovalent interactions, lock and key vs induced fit paradigms, and organic chemistry mechanisms for nonenzymatic formation of hemoglobin HbA1c and carbamylated hemoglobin, CHb) into a practical and tangible medical application.