Better Biochemistry: Fischer Projections

Biochemistry is a three-dimensional subject but most of us aren't comfortable thinking in three dimensions. For example, we often have difficulty envisaging how a three-dimensional substrate binds to a three-dimensional enzyme.

The problem is exacerbated because we usually teach in two dimensions for simplicity—especially in textbooks.¹ There are certain rules that have to be followed when displaying a three-dimensional object on a two-dimensional page. This is especially true for metabolites where the stereochemistry is crucial. One of these rules is called the Fischer projection.²

Most students (and faculty) don't understand the relationship between a two-dimensional Fischer projection and the three-dimensional molecule it's supposed to represent. This is unfortunate because it means they don't really understand the three-dimensional conformation of metabolites.

Let's look at a simple three-carbon compound—glyceraldehyde. There are two different versions of glyceraldehyde: D-glyceraldehyde and L-glyceraldehyde. The two different molecules cannot be superimposed, that's why you know that they are different molecules. Enzymes can tell the difference; that's why D-glyceraldehyde is a common metabolite and L-glyceraldehyde is rarely found in cells.

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