Promiscuous enzymes generating d-amino acids in mammals: Why they may still surprise us?

Abstract

Promiscuous catalysis is a common property of enzymes, particularly those using pyridoxal 5′-phosphate as a cofactor. In a recent issue of this journal, Katane et al. Biochem. J. 477, 4221–4241 demonstrate the synthesis and accumulation of d-glutamate in mammalian cells by promiscuous catalysis mediated by a pyridoxal 5′-phosphate enzyme, the serine/threonine dehydratase-like (SDHL). The mechanism of SDHL resembles that of serine racemase, which synthesizes d-serine, a well-established signaling molecule in the mammalian brain. d-Glutamate is present in body fluids and is degraded by the d-glutamate cyclase at the mitochondria. This study demonstrates a biochemical pathway for d-glutamate synthesis in mammalian cells and advances our knowledge on this little-studied d-amino acid in mammals. d-Amino acids may still surprise us by their unique roles in biochemistry, intercellular signaling, and as potential biomarkers of disease.

Mammalian D‐Cysteine: A new addition to the growing family of biologically relevant D‐amino acids

“…PLP‐dependent enzymes are prone to promiscuity in catalysis 10 . SR exhibits promiscuity as it also racemizes aspartate with 40 times lower efficiency compared with serine, and there is speculation that this could be a neurotoxic byproduct 11 . Our work has shown that SR is a cysteine racemase 7 .…”

“…10 SR exhibits promiscuity as it also racemizes aspartate with 40 times lower efficiency compared with serine, and there is speculation that this could be a neurotoxic byproduct. 11 Our work has shown that SR is a cysteine racemase. 7 Cysteine is unique among the amino acids in that there are additional isomers including side chain modifications.…”

D-Glutamate Production by Stressed Escherichia Coli Provides a Clue for the Induction Mechanism of the ALS Disease

“…Prior studies of exogenous D-glutamate suggest that it is being metabolized by dietary enzymes and bacterial ora 26 -28 . In eukaryotic cells, D-glutamate is metabolized within the mitochondria and chloroplasts (ancient prokaryote) [28][29][30][31] .…”