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

FEBS Letters

Nishijima, Masahiro¹  Hanada, Kentaro¹  Hara, Tomoko¹ 

[1] Department of Biochemistry and Cell Biology, National Institute of Infectious Diseases, 1-23-1, Toyama, Shinjuku-ku, Tokyo 162-8640, Japan

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;   

DOI  :  10.1016/S0014-5793(00)01579-9

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 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.

【 授权许可】

Unknown