Dunlop David S, Neidle Amos
Nathan Kline Institute for Psychiatric Research, 140 Old Orangeburg Road, Orangeburg, NY 10962, USA.
Brain Res Mol Brain Res. 2005 Feb 18;133(2):208-14. doi: 10.1016/j.molbrainres.2004.10.027.
The effects of various amino acids on the activity of serine racemase, purified from mouse brain, were examined. Those acting as inhibitors included compounds with electron withdrawing groups on the beta-carbon of alanine (beta-halo-alanines and L-serine-O-sulfate), which can act as enzyme-activated inhibitors, and compounds containing beta-SH groups (cysteine and homocysteine) which react with enzyme-bound pyridoxal phosphate to form thiazolidine derivatives. Glycine and a series of metabolites related to L-aspartic acid (L-aspartic acid, L-asparagine, and oxaloacetic acid) were also found to be competitive inhibitors of the racemase. The Ki values for glycine and aspartic acid inhibition were 0.15 and 1.9 mM, respectively, indicating that alterations in the concentrations of these amino acids might play a role in the regulation of D-serine synthesis.
研究了各种氨基酸对从小鼠脑中纯化的丝氨酸消旋酶活性的影响。作为抑制剂的氨基酸包括在丙氨酸β-碳上带有吸电子基团的化合物（β-卤代丙氨酸和L-丝氨酸-O-硫酸盐），它们可作为酶激活抑制剂，以及含有β-SH基团的化合物（半胱氨酸和高半胱氨酸），这些化合物与酶结合的磷酸吡哆醛反应形成噻唑烷衍生物。还发现甘氨酸和一系列与L-天冬氨酸相关的代谢物（L-天冬氨酸、L-天冬酰胺和草酰乙酸）是消旋酶的竞争性抑制剂。甘氨酸和天冬氨酸抑制的Ki值分别为0.15和1.9 mM，表明这些氨基酸浓度的变化可能在D-丝氨酸合成的调节中起作用。
