Sphingolipids metabolic pathways

Inhibition of other enzymes in the sphingolipid metabolic pathway by natural products... 

For most of the enzymes in the sphingolipid metabolic pathways, further investigation is required to elucidate their biochemical properties, such as substrate specificity, cofactor requirements, intracellular localization, and mechanisms of regulation. Emerging evidence has begun to link the regulation of some of these enzymes to the action of growth factors, cytokines and intracellular redox state. 

T. Kolter and K. Sandhoff, Sphingolipids—their metabolic pathways and the pathobiochem-istry of neurodegenerative diseases, Angew. Chem. Int. Ed., 38 (1999) 1532-1568. 

Kolter T, Sandhoff K (1999) Sphingolipids—their metabolic pathways and the pathobiochemistry of neurodegenerative diseases. Angew Chem Int Ed Engl 38 1532... 

The sphingolipid pathway has many sites at which inhibitors may be directed to bring about the pharmacologic manipulation of sphingolipid metabolism. As ceramide has a central role in a... 

Figure 8 Outline of the sphingolipid biosynthetic pathway. Natural and synthetic inhibitors of sphingolipid-metabolizing enzymes are shown adjacent to the inverted T bars.

Kitatani, K., Idkowiak-Baldys, J. Hannun, Y. A. The sphingolipid salvage pathway in ceramide metabolism and signaling. Cell Signal (2007) PMID 18191382... 

Many of the features of pathways for sphingolipid metabolism are reasonably well characterized and genes have been identified for many of the initial biosynthetic steps [20]. 

FICURE21.14 Partial metabolic pathway associated with sphingolipids. The number in the boxes eorresponds to the EC name for the biosynthetic enzyme responsible for the transformation. 

This section will address the most commonly used experimental approaches and tools that are available to probe ceramide-mediated functions. It should be noted at the outset that the interconnected metabolism of sphingolipids complicates the study of ceramide bioactivity, since ceramide participates in a network of metabolic pathways that connect several bioactive lipids, including sphingosine, sphingosine-1-phosphate, diacylglycerol and others. 

---