Compartmentation of GAPDH

The concept of the cytosol as a space that contains discrete zones of metabolites is discussed relative to the contribution of GAPDH. GAPDH is directed to very specific cell compartments. This chapter describes the utilization of GAPDH’s enzymatic function for focal demands (i.e. ATP/ADP and NAD+/NADH), and offers a speculative role for GAPDH as perhaps moderating local concentrations of inorganic phosphate and hydrogen ions (i.e. co-substrate and co-product of the glycolytic reaction, respectively). Where known, the structural features of the binding between GAPDH and the compartment components are discussed. The nuances, which are associated with the intracellular distribution of GAPDH, appear to be specific to the cell-type, particularly with regards to the various plasma membrane proteins to which GAPDH binds. The chapter includes discussion on the curious observation of GAPDH being localized to the external surface of the plasma membrane in a human cell type. The default perspective has been that GAPDH localization is synonymous with compartmentation of glycolytic energy. The chapter discusses GAPDH translocation to the nucleus and to non-nuclear cellular structures, emphasizing its glycolytic function. Nevertheless, it is becoming clear that alternate functions of GAPDH play a role in compartmentation, particularly in the translocation to the nucleus.