title: Is D-aspartate produced by glutamic-oxaloacetic transaminase-1 like 1 (Got1l1): a putative aspartate racemase?
abstract: D-Aspartate is an endogenous free amino acid in the brain, endocrine tissues, and exocrine tissues in mammals, and it plays several physiological roles. In the testis, D-aspartate is detected in elongate spermatids, Leydig cells, and Sertoli cells, and implicated in the synthesis and release of testosterone. In the hippocampus, D-aspartate strongly enhances N-methyl-D-aspartate receptor-dependent long-term potentiation and is involved in learning and memory. The existence of aspartate racemase, a candidate enzyme for D-aspartate production, has been suggested. Recently, mouse glutamic-oxaloacetic transaminase 1-like 1 (Got1l1) has been reported to synthesize substantially D-aspartate from L-aspartate and to be involved in adult neurogenesis. In this study, we investigated the function of Got1l1 in vivo by generating and analyzing Got1l1 knockout (KO) mice. We also examined the enzymatic activity of recombinant Got1l1 in vitro. We found that Got1l1 mRNA is highly expressed in the testis, but it is not detected in the brain and submandibular gland, where D-aspartate is abundant. The D-aspartate contents of wild-type and Got1l1 KO mice were not significantly different in the testis and hippocampus. The recombinant Got1l1 expressed in mammalian cells showed L-aspartate aminotransferase activity, but lacked aspartate racemase activity. These findings suggest that Got1l1 is not the major aspartate racemase and there might be an as yet unknown D-aspartate-synthesizing enzyme.
authors.affiliation: Department of Molecular Neuroscience, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, 930-0194, Japan.
authors.forename: Ayumi
authors.initials: A
authors.lastname: Tanaka-Hayashi
authors.forename: Shuuhei
authors.initials: S
authors.lastname: Hayashi
authors.forename: Ran
authors.initials: R
authors.lastname: Inoue
authors.forename: Tomokazu
authors.initials: T
authors.lastname: Ito
authors.forename: Kohtarou
authors.initials: K
authors.lastname: Konno
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Yoshida
authors.forename: Masahiko
authors.initials: M
authors.lastname: Watanabe
authors.forename: Tohru
authors.initials: T
authors.lastname: Yoshimura
authors.forename: Hisashi
authors.initials: H
authors.lastname: Mori
mesh_terms: D000591:Amino Acid Isomerases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000201:enzymology / Q000378:metabolism; D026603:D-Aspartic Acid / Q000378:metabolism*; D005260:Female; D006624:Hippocampus / Q000201:enzymology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D013737:Testis / Q000201:enzymology / Q000378:metabolism
chemical_list: D026603:D-Aspartic Acid; D000591:Amino Acid Isomerases; C000601704:Got1l1 protein, mouse; C019749:aspartate racemase