Ceramides, sphingolipid synthesis

The synthesis of all sphingolipids begins with the production of ceramide. Sphingolipids are degraded within lysosomes by specific hydrolytic enzymes. 

BIO CG4016 TACGTG- CCCT +267 serine C-palmitoyltransferase [SPT] amino transferases class-II committed rxn in sphingolipid synthesis ceramide synthesis h = SPTl (1.3e-120) w = C23H3.4 (3.0e-110) F43H9.2 (2e-36) 20, 21... 

Ceramide is generated de nooo in the endoplasmic reticulum. The first step in the biosynthesis of ceramide is the condensation of L-serine and palmitoyl-CoA, a reaction catalyzed by serine palmitoyltransferase. The condensation product obtained is 3-ketosphinganine (Fig. 3.10), and this reaction is considered as the rate-limiting enzyme in sphingolipid synthesis. ... 

Gatt, S., 1963, Enzymatic hydrolysis of sphingolipids. 1. Hydrolysis and synthesis of ceramides by an enzyme from rat brain. J. Biol. Chem. 238 3131-3133. 

Figure 21-6 Pathways of synthesis and metabolism of sphingolipids. Gray arrows indicate catabolic pathways. See also Fig. 20-11. The green extension on the ceramide structure is that of a long-chain co-hydroxyceramide that is covalently bound to protein in human skin.

Ceramide formed in mammalian systems is metabolized to sphingomyelin, glycosphingolipids, and ceramide 1-phosphate by the actions of sphingomyelin synthase, glucosylceramide synthase, and ceramide kinase on ceramide, respectively. Ceramide synthesized in the endoplasmic reticulum is transported to the Golgi apparatus for synthesis of complex sphingolipids (93). Sphingomyelin is synthesized from ceramide by transfer of the... 

Figure 26.3. Synthesis of Sphingolipids. Sphingosine is converted into ceramide, which is an intermediate in the formation of sphingomyelin and gangliosides.

Figure 6-15. Synthesis of sphingolipids. NANA = W-acetylneuraminic acid G/c = glucose Gal = galactose GalNAc = N-acetylgalactosamine PIP = pyridoxal phosphate FA = fatty acyl groups derived from fatty acids = hydrophobic chains of ceramide. The dashed box contains the portion of ceramide derived from serine.

Sphingolipid biosynthesis is catalyzed by membrane-bound enzymes of the endoplasmic reticulum. Sphingo-sine, an acylaminoalcohol, is synthesized from palmitoyl-CoA and serine in a reaction that requires pyridoxal phosphate, NADPH, and Mn + (Figure 19-7). The exact pathway of ceramide synthesis is not known. The acyl group may be added to the 2-amino group of sphinganine,... 

Synthesis of glycosphingolipids and sulfoglycosphin-golipids involves the addition of sugar and sulfate residues to ceramide from UDP-sugar derivatives or the activated sulfate donor 3 -phosphoadenosine-5 -phosphosulfate (Chapter 17), and appropriate transferases. These pathways are discussed in Chapter 16. Catabolism of sphingolipids is by specific lysosomal hydrolases. Several inherited disorders associated with the deficiencies of these enzymes are discussed below. 

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