Reversible ligand binding reactions: Why do biochemistry students have trouble connecting the dots?

Adaptive chemical behavior is essential for an organism's function and survival, and it is no surprise that biological systems are capable of responding both rapidly and selectively to chemical changes in the environment. To elucidate an organism's biochemistry, its chemical reactions need to be characterized in ways that reflect the normal physiology in vivo. This is a challenging experimental problem because biological systems are inherently complex with myriads of interlinked chemical networks orchestrating processes that are mostly irreversible in nature. One successful approach for simplifying the study of biochemical reactions is to analyze them under controlled reversible equilibrium conditions in vitro that approximate the range of physiological conditions found in vivo. Because this approach has helped elucidate some of the chemical mysteries of complex biological systems, many topics presented in modern biochemistry courses are essentially rooted in the chemistry of reversible equilibrium reactions. Since most undergraduate biochemistry courses typically require students to complete year-long general and organic chemistry courses, biochemistry instructors may assume that entering students have sufficient understanding of basic reversible equilibrium chemistry to move forward into more advanced biochemical topics. However, this assumption is at odds with our experience in that many entering students seem confused by the conventions, language, symbolic formalism, and/or mathematical tools normally use to describe reversible equilibrium reactions. Part of the problem here may stem from how certain basic chemical concepts are taught (or are not taught) in their prerequisite chemistry courses. Here, we identify some conceptual barriers that many students seem to confront and we discuss instructional strategies designed to help students "connect the dots," so to speak, and better understand how dynamic biological processes can be analyzed in terms of reversible equilibrium chemistry.