Ceramide phosphocholines (sphingomyelins) (SP0301)

From LipidomicsWiki

(Redirected from Sphingomyelin)
Jump to: navigation, search

Contents

Basics

Sphingomyelin (SM) in mammalian cells has been found to colocalize with cholesterol mainly in the plasma membrane, in lysosomal and Golgi membranes, as well as in the polar surface of circulating lipoproteins (Merrill and Jones, 1990, Koval and Pagano, 1991). In plasma lipoproteins sphingomyelin is the second most abundant polar lipid after phosphatidylcholine. It interacts strongly with cholesterol. Due to its unique physicochemical properties, SM is enriched in specialized lipid microdomains such as rafts and caveolae. Turnover of sphingomyelin is a critical process and influences the maintenance of membrane integrity and synthesis of new membranes (van Blitterswijk et al. 2001).

Structure

Sphingomyelin
Sphingomyelin

Natural sources

Sphingomyelin and related lipids

Nomenclature

IUPAC

Sphingolipid classes and subclasses


Biosynthesis and metabolic pathways

Sphingomyelin synthesis de novo is mediated by sphingomyelin synthase, which transfers the phosphorylcholine moiety from phosphatidylcholine (PC) onto ceramide forming sphingomyelin and diacylglycerol (DAG) (Ullman, Radin, 1974). This enzyme is also able to catalyse the reverse reaction and generate phosphatidylcholine from sphingomyelin and DAG (Marggraf et al. 1981). Recently, a novel family of membrane proteins responsible for SM synthesis has been identified (Huitema et al. 2004). Two members of this family SMS1 and SMS2 fulfill the criteria for functional sphingomyelin synthase. SMS1 seems to represent the well-known Golgi-associated SM synthase while SMS2 is located to the plasma membrane. This fact needs further explanations since the presence of sphingomyelin synthase in the plasma membrane may impair ceramide signalling by converting ceramide back to sphingomyelin and generating diacylglycerol.

Sphingomyelin synthesized in the Golgi is transported to the plasma membrane via vesicular transport (Diringer et al. 1972).

The degradation of sphingomyelin leads to the release of ceramide and free sphingosine, known signalling molecules. However, aside from generation of second messengers, stimulation of sphingomyelin hydrolysis has been shown to induce cholesterol movement from the cell surface to intracellular membranes (Koval and Pagano 1991). This suggests that sphingomyelin metabolism plays an essential role not only in signalling pathways but also in the alteration of membrane physical properties.

Sphingomyelinases

Sphingomyelinases, enzymes catalysing hydrolysis of sphingomyelin, have been classified into five categories based upon their pH optima, cellular localization, and cation dependence.

The neutral membrane-bound Mg2+-independent sphingomyelinase (N-SMase) and the lysosomal acid sphingomyelinase (A-SMase) have been the best studied for their roles in ceramide generation. An increase in N-SMase activity, a corresponding decrease in SM, and an increase in ceramide have been demonstrated in response to TNFα, Fas ligand, 1α,25-dihydroxyvitamin D3, γ-interferon, chemotherapeutic agents, heat stress, ischemia/ reperfusion, and interleukin-1 (Liu et al. 1998, Tepper et al. 1995). In addition, both arachidonic acid and glutathione depletion have been shown to activate this enzyme (Liu et al. 1998, Jayadev et al. 1997, Levade et al.1994/1999). The acid sphingomyelinase gene codes for both lysosomal (cation-independent) and secretory sphingomyelinase (fully or partially dependent on Zn+² for enzymatic activity) (Schissel et al., 1998b). Abnormalities in sphingomyelin metabolism have been associated with atherosclerosis, cancer and genetic disorders (e.g. Niemann-Pick disease).

Methods

Personal tools
Create a book