A method has been developed based on the osmotic sensitivity of protoplasts, that permits turbidimetrical estimation of the penetration of non-metabolizable compounds into yeast protoplasts. Using this method a wide variety of sugars and related compounds have been tested as presumptive substrates for the constitutive hexose transport system in baker's yeast. An integration of the results obtained by this method with those obtained by other approaches has led to the establishment of the structural requirements that a compound has to meet in order to be transported. The basic structural requirement seems to be met by a pyranose ring for glucose and a furanose ring for fructose. With compounds that can be regarded as structurally related to d-glucopyranose, there is a broad tolerance for modifications at carbons 1 and 2, and somewhat less so for modifications at carbon 3. Similar requirements, except for carbon 2, apply to compounds that can be regarded as structurally related to D-fructofuranose.
Physical diffusion of sugars, and related compounds, through the cell membrane of baker's yeast is very low, so that they only can enter into the cell at measurable rates by means of specific transport devices. The factor by which the entrance of glucose is increased over its physical diffusion, at concentrations in the millimolar range, is of the order of 106.