Sphingolipid Metabolic Pathway: An Overview of Major Roles Played in Human Diseases

Figure 3

Hypothetical compartmentalization of sphingolipid metabolism. Reactions in the sphingolipid metabolic pathway can be isolated into different hypothetical compartments with each compartment representing ceramide either as a substrate or product of the reactions. Compartment C-1 is a de novo ceramide synthesis channel, compartment C-2 represents reactions leading to synthesis of complex sphingolipids, compartment C-3 is comprised of reaction leading to hydrolytic generation of ceramide from sphingomyelin, and compartment C-4 represents reactions in which ceramide is converted into other intermediates like sphingosine-1-phosphate and ceramide-1-phosphate. Activities/status of each compartment can be translated into different physiological events; accumulation of ceramide due to increased production of ceramide in C-1 would result in ER stress, increased generation of ceramide-1 phosphate, and sphingosine-1-phosphate in compartment C-4 results in progrowth and proinflammatory scenario in the cell. In different disease conditions, the status of each of these compartments contributes to the overall pathology of the disease.