D-amino acids in the brain: the biochemistry of brain serine racemase.
It has been recently established that in various brain regions D-serine, the product of serine racemase, occupies the so-called 'glycine site' within N-methyl D-aspartate receptors. Mammalian brain serine racemase is a pyridoxal-5' phosphate-containing enzyme that catalyzes the racemization of L-serine to D-serine. It has also been shown to catalyze the alpha,beta-elimination of water from L-serine or D-serine to form pyruvate and ammonia. Serine racemase is included within the group of type II-fold pyridoxal-5' phosphate enzymes, together with many other racemases and dehydratases. Serine racemase was first purified from rat brain homogenates and later recombinantly expressed in mammalian and insect cells as well as in Escherichia coli. It has been shown that serine racemase is activated by divalent cations like calcium, magnesium and manganese, as well as by nucleotides like ATP, ADP or GTP. In turn, serine racemase is also strongly inhibited by reagents that react with free sulfhydryl groups such as glutathione. Several yeast two-hybrid screens for interaction partners identified the proteins glutamate receptor interacting protein, protein interacting with C kinase 1 and Golga3 to bind to serine racemase, having different effects on its catalytic activity or stability. In addition, it has also been proposed that serine racemase is regulated by phosphorylation. Thus, d-serine production in the brain is tightly regulated by various factors pointing at its physiologic importance. In this minireview, we will focus on the regulation of brain serine racemase and d-serine synthesis by the factors mentioned above.
Departamento de Bioquímica y Biología Molecular, Facultad de Ciencias Químicas, Universidad Complutense de Madrid, Spain.
Florian
F
Baumgart
Ignacio
I
Rodríguez-Crespo
D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000201:enzymology*; D002352:Carrier Proteins / Q000378:metabolism; D002413:Cations, Divalent / Q000737:chemistry; D006801:Humans; D008969:Molecular Sequence Data; D009569:Nitric Oxide / Q000378:metabolism; D009711:Nucleotides / Q000737:chemistry; D019998:Racemases and Epimerases / Q000737:chemistry* / Q000378:metabolism*; D051381:Rats; D012694:Serine / Q000096:biosynthesis* / Q000737:chemistry; D000099300:Serine Racemase
D002352:Carrier Proteins; D002413:Cations, Divalent; D009569:Nitric Oxide; D009711:Nucleotides; D019998:Racemases and Epimerases; D012694:Serine; D000099300:Serine Racemase