Eukaryotic serine racemase (SR) is a pyridoxal 5′-phosphate enzyme belonging to the Fold-type II group, which catalyzes serine racemization and is responsible for the synthesis of D-Ser, a co-agonist of the N-methyl-d-aspartate receptor. In addition to racemization, SR catalyzes the dehydration of D- and L-Ser to pyruvate and ammonia. The bifuctionality of SR is thought to be important for D-Ser homeostasis. SR catalyzes the racemization of D- and L-Ser with almost the same efficiency. In contrast, the rate of L-Ser dehydration catalyzed by SR is much higher than that of D-Ser dehydration. This has caused the argument that SR does not catalyze the direct D-Ser dehydration and that D-Ser is first converted to L-Ser, then dehydrated. In this study, we investigated the substrate and solvent isotope effect of dehydration of D- and L-Ser catalyzed by SR from Dictyostelium discoideum (DdSR) and demonstrated that the enzyme catalyzes direct D-Ser dehydration. Kinetic studies of dehydration of four Thr isomers catalyzed by D. discoideum and mouse SRs suggest that SR discriminates the substrate configuration at C3 but not at C2. This is probably the reason for the difference in efficiency between L- and D-Ser dehydration catalyzed by SR.

真核生物丝氨酸消旋酶（SR）是属于Fold型II组的吡ido醛5'-磷酸酶，催化丝氨酸消旋作用，并负责合成D-Ser（N-甲基-d的共激动剂）-天冬氨酸受体。除外消旋作用外，SR还催化D-和L-Ser脱水成丙酮酸和氨。SR的双向作用被认为对D-Ser稳态很重要。SR以几乎相同的效率催化D-Ser和L-Ser的外消旋作用。相反，SR催化的L-Ser脱水速率远高于D-Ser的脱水速率。这引起了这样的论点，即SR不催化直接的D-Ser脱水，而D-Ser首先被转化为L-Ser，然后脱水。在这项研究中，我们研究了衬底和通过从SR催化D-和L-丝氨酸的脱水溶剂同位素效应粘菌（DdSR）和证明了酶催化直接d-SER脱水。四种催化的Thr异构体脱水的动力学研究。D. discoideum和小鼠SR提示SR可以区分C3处的底物构型，但不能区分C2处的底物构型。这可能是SR催化L-和D-Ser脱水效率不同的原因。