Biomaterial Database

Regulation of phospholipase C delta activity by sphingomyelin and sphingosine. 1992

T Pawelczyk, and J M Lowenstein

Graduate Department of Biochemistry, Brandeis University, Waltham, Massachusetts 02254.

Phospholipase C delta (PLC delta) is strongly inhibited by sphingomyelin (SM). The inhibition occurs in both the presence and the absence of spermine, an activator of PLC delta. Phosphatidylethanolamine (PE), phosphatidylcholine (PC), phosphatidylserine (PS), and phosphatidylinositol (PI) also inhibit PLC delta in the presence of spermine but are much less effective than SM. PE and PC activate and PS and PI inhibit PLC delta in the absence of spermine. Again, the inhibition by PS and PI is much weaker than the inhibition observed with SM. Similar or identical effects are observed in detergent micelle and liposome assays. Comparisons of physiological concentrations of SM with concentrations yielding 50% inhibition of PLC delta in vitro indicate that SM is likely to be a major factor in regulating the activity of PLC delta by inhibition. It is proposed that, in vivo, sphingomyelin acts as an inhibitor of PLC delta, which enables the enzyme to be regulated by activation. In certain circumstances, there is a substantial decline in SM and this may lead to a partial relief of the inhibition. PLC delta is activated by sphingosine in the absence of spermine. However, this activation occurs at unphysiologically high concentrations of sphingosine. The effects of SM and sphingosine on PLC delta in marked contrast to those observed with protein kinase C, which is unaffected by sphingomyelin and inhibited by sphingosine.

UI	MeSH Term	Description	Entries
D007527	Isoenzymes	Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.	Alloenzyme,Allozyme,Isoenzyme,Isozyme,Isozymes,Alloenzymes,Allozymes
D007700	Kinetics	The rate dynamics in chemical or physical systems.
D008081	Liposomes	Artificial, single or multilaminar vesicles (made from lecithins or other lipids) that are used for the delivery of a variety of biological molecules or molecular complexes to cells, for example, drug delivery and gene transfer. They are also used to study membranes and membrane proteins.	Niosomes,Transferosomes,Ultradeformable Liposomes,Liposomes, Ultra-deformable,Liposome,Liposome, Ultra-deformable,Liposome, Ultradeformable,Liposomes, Ultra deformable,Liposomes, Ultradeformable,Niosome,Transferosome,Ultra-deformable Liposome,Ultra-deformable Liposomes,Ultradeformable Liposome
D008099	Liver	A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.	Livers
D010738	Type C Phospholipases	A subclass of phospholipases that hydrolyze the phosphoester bond found in the third position of GLYCEROPHOSPHOLIPIDS. Although the singular term phospholipase C specifically refers to an enzyme that catalyzes the hydrolysis of PHOSPHATIDYLCHOLINE (EC 3.1.4.3), it is commonly used in the literature to refer to broad variety of enzymes that specifically catalyze the hydrolysis of PHOSPHATIDYLINOSITOLS.	Lecithinase C,Phospholipase C,Phospholipases, Type C,Phospholipases C
D010743	Phospholipids	Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides see GLYCEROPHOSPHOLIPIDS) or sphingosine (SPHINGOLIPIDS). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system.	Phosphatides,Phospholipid
D011189	Potassium Chloride	A white crystal or crystalline powder used in BUFFERS; FERTILIZERS; and EXPLOSIVES. It can be used to replenish ELECTROLYTES and restore WATER-ELECTROLYTE BALANCE in treating HYPOKALEMIA.	Slow-K,Chloride, Potassium
D004789	Enzyme Activation	Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.	Activation, Enzyme,Activations, Enzyme,Enzyme Activations
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D013096	Spermine	A biogenic polyamine formed from spermidine. It is found in a wide variety of organisms and tissues and is an essential growth factor in some bacteria. It is found as a polycation at all pH values. Spermine is associated with nucleic acids, particularly in viruses, and is thought to stabilize the helical structure.