D‐Serine inhibits serine palmitoyltransferase, the enzyme catalyzing the initial step of sphingolipid biosynthesis

[摘要]

Serine palmitoyltransferase (SPT), responsible for the initial step of sphingolipid biosynthesis, catalyzes condensation of palmitoyl coenzyme A and L-serine to produce 3-ketodihydrosphingosine (KDS). For determination of the stereochemical specificity of the amino acid substrate, a competition analysis of the production of [³H]KDS from L-[³H]serine was performed using purified SPT. D-Serine inhibited [³H]KDS production as effectively as non-radioactive L-serine, whereas neither D-alanine nor D-threonine showed any significant effect. Incubation of purified SPT with [palmitoyl 1-¹⁴C]palmitoyl coenzyme A and D-serine did not produce [¹⁴C]KDS, while the control incubation with L-serine did. These results suggest that D-serine competes with L-serine for the amino acid recognition site of SPT, but that D-serine is not utilized by this enzyme to produce KDS.

[学科分类] 生物化学/生物物理

[关键词] D-Serine;Serine palmitoyltransferase;Sphingolipid;CoA;coenzyme A;KDS;3-ketodihydrosphingosine;SPT;serine palmitoyltransferase;CHO;Chinese hamster ovary;IC50;the concentration which caused 50% inhibition