Murine serine racemase (SR), the enzyme responsible for the biosynthesis of the neuromodulator d-serine, was reported to form a complex with glyceraldehyde 3-phosphate dehydrogenase (GAPDH), resulting in SR inhibition. In this work, we investigated the interaction between the two human orthologues. We were not able to observe neither the inhibition nor the formation of the SR-GAPDH complex. Rather, hSR is inhibited by the hGAPDH substrate glyceraldehyde 3-phosphate (G3P) in a time- and concentration-dependent fashion, likely through a covalent reaction of the aldehyde functional group. The inhibition was similar for the two G3P enantiomers but it was not observed for structurally similar aldehydes. We ruled out a mechanism of inhibition based on the competition with either pyridoxal phosphate (PLP) – described for other PLP-dependent enzymes when incubated with small aldehydes – or ATP. Nevertheless, the inhibition time course was affected by the presence of hSR allosteric and orthosteric ligands, suggesting a conformation-dependence of the reaction.

鼠丝氨酸消旋酶（SR），负责神经调节因子d生物合成的酶据报道，β-丝氨酸与3-磷酸甘油醛脱氢酶（GAPDH）形成复合物，导致SR抑制。在这项工作中，我们调查了两个人类直系同源物之间的相互作用。我们既没有观察到SR-GAPDH复合物的抑制也没有观察到它的形成。相反，hGAPDH底物3-磷酸甘油醛（G3P）可能以时间和浓度依赖性方式抑制hSR，这可能是通过醛官能团的共价反应来实现的。两种G3P对映异构体的抑制作用相似，但对于结构相似的醛则未观察到抑制作用。我们基于与吡ido醛磷酸酯（PLP）的竞争（基于与小醛一起孵育时对其他PLP依赖性酶的描述）或ATP排除了抑制机制。不过，