Sweetness reception in man: The multipoint attachment theory

The multipoint attachment (MPA) theory assumes the presence, in the human sweetness receptor (probably a seven-pass transmembrane receptor), of at least eight fundamental recognition sites, namely, the B-, AH-, XH-, G1-, G2-, G3-, G4- and D-recognition sites. The B-recognition site is assumed to be a Lys residue; the AH- and XH-recognition sites, Asp (or Glu) residues; the G1-, G2-, G3- and G4-recognition sites, Thr residues; and the D-recognition site, a Ser (or Thr) residue. These eight recognition sites are able to interact with eight sweetener interaction sites, namely, the B, AH, XH, G1, G2, G3, G4 and D interaction sites. The number of interaction sites in a given sweetener may be equal to or lower than eight. Apart from D, the interaction sites are made up of two elementary interaction sites (interaction points or subsites). These interaction points (namely, the B1, B2, AH1, AH2, XH1, XH2, G1, Fl, G2, E2, G3, E3, G4, E4 and D points) operate with the receptor through three types of elementary interactions, namely, ionic, H-bonding and steric interactions. B (B1, B2) is an anionic group (CO2-) or an H-bond acceptor atom (Cl, Br, O); AH1, AH2, XH1, XH2 are H-bond donor groups (NH+, NH, OH); Fl, E2, E3, E4 are H-bond acceptor atoms (N, O, Cl, Br); G1, G2, G3, G4 are steric interaction subsites (CH3, CH2, CH, halogens); and D is an H-bond acceptor group (CN). Several examples are given to illustrate the theory. For example, according to the MPA theory, D-glucose is a B1, B2, AH1, AH2, XH1, XH2-type sweetener, D-fructose an F1, E2, E3, E4-type sweetener, and sucrose a B1, B2, AH1, AH2, XH1, XH2, G1, E1, G2, E2, G3, E3, G4, E4-type sweetener. Copyright (C) 1996 Elsevier Science Ltd