D-Serine inhibits serine palmitoyltransferase, the enzyme catalyzing the initial step of sphingolipid biosynthesis.
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 [(3)H]KDS from L-[(3)H]serine was performed using purified SPT. D-Serine inhibited [(3)H]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-(14)C]palmitoyl coenzyme A and D-serine did not produce [(14)C]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.
Hanada
K
K
Department of Biochemistry, National Institute of Infectious Diseases, 1-23-1, Toyama, Tokyo, Japan. hanak@nih.go.jp
Hara
T
T
Nishijima
M
M
D000217:Acyltransferases / Q000037:antagonists & inhibitors*; D000818:Animals; D001667:Binding, Competitive; D016466:CHO Cells; D006224:Cricetinae; D010171:Palmitoyl Coenzyme A / Q000378:metabolism; D012694:Serine / Q000378:metabolism / Q000494:pharmacology*; D051102:Serine C-Palmitoyltransferase; D013107:Sphingolipids / Q000096:biosynthesis*; D013110:Sphingosine / Q000031:analogs & derivatives / Q000378:metabolism; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D014316:Tritium
D013107:Sphingolipids; D014316:Tritium; C002882:ketodihydrosphingosine; D010171:Palmitoyl Coenzyme A; D012694:Serine; D000217:Acyltransferases; D051102:Serine C-Palmitoyltransferase; D013110:Sphingosine