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Introduction

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High-Yield Terms

  • Sphingolipid: a class of lipid composed of a core of the long-chain amino alcohol, sphingosine, to which is attached a polar head group (such as a sugar) and a fatty acid via N-acylation

  • Ceramide: a class of lipid composed of a sphingosine core and a single fatty acid but no polar head group as for sphingolipids

  • Spingomyelins: a class of sphingolipid that contains phosphocholine as the polar head group and are, therefore, also a class of phospholipid

  • Saposin: a family (A, B, C, and D) of small glycoprotein activators of lysosomal hydrolases that are all derived from a single precursor, prosaposin

  • Hexosaminidases: dimeric enzymes composed of 2 subunits, either the α-subunit (encoded by the HEXA gene) and/or the β-subunit (encoded by the HEXB gene); various isoforms of β-hexosaminidase result from the combination of α- and β−subunits

  • Lysosomal storage disease: any of a large family of disorder resulting from defects in lysosomal hydrolases resulting in accumulation of incompletely degraded complex lipids, particularly of the sphingolipid family

  • Cherry-red spot: a finding describing the appearance of a small circular deep red choroid shape in the fovea centralis (fundus) of the eye in a variety of lipid storage diseases

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Synthesis of Sphingosine and the Ceramides

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The sphingolipids, like the phospholipids, are composed of a polar head group and 2 nonpolar tails. The core of a sphingolipid is the long-chain amino alcohol, sphingosine (Figure 21-1). The sphingolipids include the sphingomyelins and glycosphingolipids (the cerebrosides, sulfatides, globosides, and gangliosides). Sphingomyelins are unique in that they are also phospholipids. Sphingolipids are components of all membranes but are particularly abundant in the myelin sheath.

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FIGURE 21-1:

Structure of sphingosine and a ceramide. Reproduced with permission of the medical biochemistry page, LLC.

Graphic Jump Location
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The initiation of the synthesis of the sphingoid bases (sphingosine, dihydrosphingosine, and ceramides) takes place via the condensation of palmitoyl-CoA and serine (Figure 21-2). This reaction occurs on the cytoplasmic face of the endoplasmic reticulum (ER) and is catalyzed by serine palmitoyltransferase (SPT). SPT is the rate-limiting enzyme of the sphingolipid biosynthesis pathway. Active SPT is a heterotrimeric enzyme composed of 2 main subunits and a third subunit that greatly enhances the activity of the enzyme complex as well as confers acyl-CoA preference to the complex.

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FIGURE 21-2:

Pathway for sphingosine and ceramide synthesis. Reproduced with permission of the medical biochemistry page, LLC.

Graphic Jump Location
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The acylation of dihydrosphingosine (also called sphinganine) to dihydroceramide occurs through the activities of 6 different ceramide synthases (CerS) in humans. These CerS enzymes introduce fatty acids of varying lengths and degrees of unsaturation.

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Following conversion to ceramide, sphingosine is released via the action of ceramidase. Sphingosine can be reconverted to a ceramide ...

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