D-Glutamate is metabolized in the heart mitochondria

Abstract

D-Amino acids are enantiomers of L-amino acids and have recently been recognized as biomarkers and bioactive substances in mammals, including humans. In the present study, we investigated functions of the novel mammalian mitochondrial protein 9030617O03Rik and showed decreased expression under conditions of heart failure. Genomic sequence analyses showed partial homology with a bacterial aspartate/glutamate/hydantoin racemase. Subsequent determinations of all free amino acid concentrations in 9030617O03Rik-deficient mice showed high accumulations of D-glutamate in heart tissues. This is the first time that a significant amount of D-glutamate was detected in mammalian tissue. Further analysis of D-glutamate metabolism indicated that 9030617O03Rik is a D-glutamate cyclase that converts D-glutamate to 5-oxo-D-proline. Hence, this protein is the first identified enzyme responsible for mammalian D-glutamate metabolism, as confirmed in cloning analyses. These findings suggest that D-glutamate and 5-oxo-D-proline have bioactivities in mammals through the metabolism by D-glutamate cyclase.

Gut microbiota–derived D-serine protects against acute kidney injury

“…gut were the primary microbial products (12) and that they played physiologic roles in the central nervous system (13), heart (14), and skin (15). However, the precise roles of the gut microbiota-associated D-amino acids in kidney diseases have yet to be revealed.…”

Analysis of BMAA enantiomers in cycads, cyanobacteria, and mammals: in vivo formation and toxicity of d-BMAA

“…Although D-amino acids are important in neurochemistry, their occurrence and the presence of enzymes involved in their racemisation and metabolism can be found in other tissues. The presence of D-glutamate in the heart (Ariyoshi et al 2017), and D-aspartate and D-serine in tissues such as the testes, kidney, skin and skeletal system have been documented (Guevara and Mani, 2016;Ito et al 2016).…”

Secreted d‐aspartate oxidase functions in C. elegans reproduction and development

“…In DDO‐deficient mice, the levels of d ‐Asp in brain tissues, peripheral tissues, and physiological fluids are much higher than those in wild‐type mice, whereas the amounts of d ‐Glu in the kidney and liver do not differ significantly . On the other hand, we recently demonstrated that a novel mitochondrial gene, 9030617O03Rik , encodes d ‐Glu cyclase, which reversibly converts d ‐Glu to 5‐oxo‐ d ‐proline, and that d ‐Glu content is significantly higher in d ‐Glu cyclase‐deficient mouse hearts than in wild‐type mouse hearts . Thus, in mammals d ‐Glu is degraded by d ‐Glu cyclase, but not by DDO.…”