Occurrence and Biosynthesis of Ceramide Phosphorylethanolamine in Chicken and Rat Liver

Abstract

Ceramide phosphorylethanolamine has been found to occur in chicken and rat liver. An enzyme (CDP-ethanolamine:ceramide ethanolaminephosphotransferase) has been found in a number of tissues which catalyzes the biosynthesis of this lipid. The enzyme catalyzes the transfer of the phosphorylethanolamine moiety of CDP-ethanolamine to the free primary hydroxyl group of a ceramide (N-acylsphingosine). The chicken liver enzyme requires 0.010 M manganese ions for optimal activity and has a pH optimum of 7.7. The Km for the substrate N-octanoyl-threo-sphingosine was found to be 2.5 × 10−4 M. A study of the effect of increasing CDP-ethanolamine concentration on the reaction rate indicates from sigmoid kinetics that the coenzyme modulates and possibly regulates PE-ceramide transferase activity. The enzyme differs from sphingomyelin synthetase (CDP-choline:ceramide cholinephosphotransferase) in that it will only utilize the unnatural threo isomer of N-acylsphingosines (threo-ceramides) as acceptors for the phosphorylethanolamine moiety of CDP-ethanolamine. Sphingomyelin synthetase has been shown to utilize erythro-ceramides the presence of sulfhydryl reagents (Sribney, M.: Can. J. Biochem. 49, 306 (1971)); the enzyme catalyzing the biosynthesis of ceramide phosphorylethanolamine, however, does not do so, even in the presence of a variety of sulfhydryl reagents tested.

Both Sphingomyelin Synthases SMS1 and SMS2 Are Required for Sphingomyelin Homeostasis and Growth in Human HeLa Cells

“…An alternative explanation could be that mammalian cells are equipped with an SMS-independent pathway of SM synthesis. For example, Muehlenberg et al (37) proposed a pathway of SM synthesis in which ceramide is first converted to ethanolamine phosphorylceramide (EPC) via transfer of the head group from PE. EPC is then converted to SM by stepwise methylation in a reaction analogous to the S-adenosylmethionine-dependent conversion of PE to PC.…”

The Multigenic Sphingomyelin Synthase Family

“…Because the reactions are reversible, these enzymes simultaneously control the balance between phosphoglycerolipids and phosphosphingolipids on one hand and between ceramide and DAG on the other. In the same way that PE can be converted into PC by a triple methylation, Muehlenberg et al (11) proposed that EPC can be methylated to form SM. This alternative pathway of SM synthesis has been detected in rat liver and brain microsomes (12,13).…”

Lipidomic Analysis of Toxoplasma gondii Reveals Unusual Polar Lipids

“…This reaction might be catalyzed by a protozoan-encoded protein or could conceivably be due to an upregulation of the synthesis of PE-cer by the host as a result of the commensal interaction or parasite infection, as this lipid is known to occur at low levels in mammalian cells (36,37 In the study by Fouts and Boothroyd (38), a human gene encoding a phosphoserine aminotransferase 1 (AI015679) is shown to be repressed in tachyzoite infected HFF cells. Suppression of phosphoserine aminotransferase (if confirmed) would support the diversion of the phosphoserine metabolism toward serine production.…”