Strange Amino Acid Made in Brain

Researchers have identified the first amino acid with a right-handed twist known to be made by higher mammals. They cloned a gene involved in making the amino acid, rounding out their case that this molecule plays a central role in learning and memory.

The team, led by neuroscientist Solomon Snyder of the Johns Hopkins University School of Medicine, had previously implicated the amino acid, called D-serine, as an activator of the so-called NMDA receptor--a structure in neurons that plays a pivotal role in learning, brain growth, and brain cell death. But D-serine is a right-handed amino acid, a mirror image of all other known molecules made by mammals. The idea that the molecule acts on the NMDA receptor was so radical, Snyder concedes, that people "paid no attention" to it.

To nail D-serine's origin to the brain, Snyder's team went after the enzyme that makes it. They cloned the gene for serine racemase and showed that it is active in the same cells in the brains of rats that harbor D-serine, they report in the 9 November Proceedings of the National Academy of Sciences. They also showed that destroying D-serine in the rat brain greatly reduces NMDA receptor activity.

"It's a significant advance," says neuroscientist Joseph Coyle of Harvard Medical School. "They've now characterized at a molecular level a key new participant in NMDA receptor function." Medicine should benefit, Snyder says, as the newly cloned enzyme, called serine racemase, provides a novel target for drugs to treat neurological conditions in which NMDA receptors play a role, such as anxiety, epilepsy, and damage from strokes.