Evidence for the proximity of sweet and bitter receptor sites

Abstract

ALTHOUGH sweetness and bitterness are generally referred to as two of the common or basic tastes, it is by no means certain that they are, in fact, primary¹. Furthermore, neuro-physiological evidence has shown that response to several of the basic taste stimuli can occur in a single taste cell². Much structural progress in the chemistry of sweetness has been made in the past decade through Shallenberger's hypothesis^3–5 that the sweetness of sugars depends on hydrogen bonds between the sugar molecule and receptor site. Our previous work^6–9 has indicated that sugar molecules and their simple derivatives are nearly always sweet, bitter or bitter–sweet. Bitter–sweet sugar molecules, like certain artificial sweeteners such as saccharin, have both bitterness and sweetness as intrinsic features of their molecules¹⁰—neither response can be altered by exhaustive stepwise purification of such compounds¹⁰. Bitter–sweet sugar molecules appear to be ‘polarised’ on taste receptors⁹ so that one end of the molecule binds to sweet receptor sites and the other to bitter receptor sites. It is not clear, however, whether these molecules distribute themselves, some on sweet receptors and some on bitter receptors, or whether a single molecule can span both sweet and bitter receptor sites simultaneously. We now report an experiment designed to distinguish between these possibilities, using a typical bitter–sweet and conformationally defined glycoside, methyl-α-D-mannopyranoside (Fig. 1.).