Carvone: through the looking glass

No one could mistake the pungent, spicy smell of caraway on rye bread, or perhaps in a yoghurt pudding, for the sharp, fresh smell of spearmint pinched from the garden or flavouring your tea. The two are entirely distinct. And yet the chemicals that make these two smells are identical in every possible way, except that they are mirror images of each other (‘enantiomers’).

As Alice learned rather quickly, which side of the mirror you are on is extremely important. To understand why two nearly identical chemicals would be so different from one another, consider your left and right hands. They have identical structures, but are mirror images of each other. So your right hand can fit into and shake another right hand naturally, and the same goes for the left – but no matter which way you move, twist or change, your left hand cannot shake your (or anyone else’s) right hand in quite the same way.

It is the same with molecules. With enough different components, molecules can form mirror-image versions. There are usually two (as in right-handed and left-handed), but for really complicated molecules there can be more, with subcomponents being reflections of one another. Physical chemical processes often produce a mixture of these mirror images, but in biology, a particular process will only make one of the two forms.

In amino acids and sugars, these chiral forms are traditionally labelled ‘D’ or ‘L’. Just about every other kind of compound is given the more general ‘R’ and ‘S’ labels. They could just as easily be called “Right handed” or “Left handed” forms.

The handshake of life

So when we refer any complex molecule, like ATP, amino acids or sugars, we’re in fact talking about only one of the mirror-image forms. Nearly all amino acids are in the “L” formation. Some enterprising bacteria go to some trouble to use the wrong “D” form of amino acids, which stymies potential attacks on their cell wall.

The workings of living systems are set up to choose between mirror-image versions of chemicals – generally, only one of the mirror image versions of a chemical is made, and recognized by the machinery of life (like two right hands shaking). Why life chooses one ‘hand’ over the other is a story for another day, but the actual chemistry is not directly affected by the mirror image – if one flipped every single molecule involved to its inverse, everything would work just the same.

Back to caraway and mint

Each and every smell receptor (like every protein molecule in our body) has a specific chirality (handedness). Because of this, each receptor senses ‘smell molecules’ in a mirror-sensitive way.

The R-carvone (spearmint) can bind to one set of smell receptors, but not to the S-carvone (caraway) receptors – just as your left hand cannot shake with the right hand. Similarly, the S-carvone binds caraway-smell receptors, which sends the ‘rye bread’ message on to the brain. Despite their chemically identical properties, they have very different homes in our smell centre.

Mix ups

When people make a chemical to work in living things, they usually create a mixture of both mirror-image forms in the test tube because we’re not as clever chemists as are bodies are.

One example of where this can be a serious problem is Thalidomide, the powerful anti-morning sickness but limb-deforming drug. It came in a mixture of R and S forms, as they are extremely difficult to isolate from one another. Tragically, one form was the useful drug while the other form caused birth defects. More recently, people have been able to purify a number of drugs into one active mirror-image form, which makes them more precise and obviously requires a far lower dosage.

On this side of the looking glass, one has to be careful of every detail.