ABSTRACT
Enzymatic substrate-inhibition was originally formulated in 1930 by Sir John Burdon Sanderson Haldane in his treatise ‘Enzymes’ (Haldane 1930) (see Section 3.2.2).
Long before scientists from other fields, including physiology, enzymologists were formulating a selfinduced inhibition by activating ligands, i.e., substrates. Evidently, inhibition can take place for enzymes at high substrate ‘agonist’ concentrations, even when feedback inhibition due to product generation is ruled out (Kaiser 1980; Kuhl 1994). Thus, no regulatory mechanism can explain the concentration-dependent attenuation of enzymatic activity at high substrate concentration ‘substrate inhibition’ other than through the substrate itself at a likely regulatory site. The result is bell-shaped dose-response curves. Similarly, ligand-induced inhibition at high concentration, which might yield bell-shaped synagics, is seen in many other fields including receptor studies (Trist & Leff 1985; Winding & Bindslev 1993; Bronnikov et al. 1999; Accomazzo et al. 2002; Hornigold et al. 2003; Schlee et al. 2006) and transport experiments with channels (Jow & Numann 1999; Murayama et al. 1999; Zwart & Vijverberg 2000; Hapfelmeier et al. 2003; Hong & Wang 2005), with pumps (Andersen et al. 2001; Bucher et al. 2005; Einholm et al. 2007), with cotransporters (Berthelot et al. 2005), with uniporters (Alpers 2005; Vieira et al. 2005), and in motor string formation (Hayashi et al. 2007).
