Racemase

Racemase is an enzyme that catalyzes the interconversion of enantiomers at a single stereogenic center in a molecule, typically converting L-enantiomers to D-enantiomers. In biochemistry, the best-known racemases act on amino acids and are essential for producing D-amino acids used in bacterial cell wall synthesis, notably D-alanine and D-glutamate.

Mechanism: Most amino acid racemases are pyridoxal phosphate (PLP)-dependent. They work by abstracting the α-hydrogen to form a planar, temporarily deprotonated intermediate, allowing reprotonation from the opposite face to yield the opposite enantiomer. Some racemases employ alternative strategies, using cysteine residues or metal cofactors.

Examples and roles: Alanine racemase and glutamate racemase are classic PLP-dependent enzymes necessary for peptidoglycan assembly in many bacteria. Proline racemase and aspartate racemase are reported in several bacteria and parasites, contributing to metabolism or virulence in some organisms. Although most studied racemases act on amino acids, enzymes with broader substrate scopes exist that racemize other chiral centers.

Occurrence and importance: Racemases are found across bacteria, archaea, and some eukaryotes. In bacteria, the availability of D-amino acids is tied to cell wall integrity and resistance to proteases. Because D-alanine and D-glutamate are unique to microbes, inhibitors of alanine racemase have been explored as potential antibiotics.

Distinction: Racemases differ from epimerases. Racemases interconvert enantiomers at a single stereocenter; epimerases typically alter configuration at a stereocenter within a molecule that contains multiple stereocenters, often via related catalytic strategies.