Sandbox Reserved 313: Difference between revisions
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{{STRUCTURE_2dds | PDB=2dds | SCENE=Sandbox_Reserved_313/2dds/1}} | {{STRUCTURE_2dds | PDB=2dds | SCENE=Sandbox_Reserved_313/2dds/1}} | ||
=Introduction= | =Introduction= | ||
'''Sphingomyelin phosphodiesterase (Sphingomyelinase):''' (SMase) is an enzyme which catalyzes the hydrolysis of sphingomyelin (SM) to [http://en.wikipedia.org/wiki/Ceramide ceramide] and [http://en.wikipedia.org/wiki/Phosphocholine phosphocholine]. This enzyme also has [http://en.wikipedia.org/wiki/Hemolytic hemolytic] activity where red blood cells are ruptured and hemoglobin is released into the blood plasma. <ref name="gp">PMID: 16595670 </ref>. SMase is a member of the DNA-I superfamily involved | '''Sphingomyelin phosphodiesterase (Sphingomyelinase):''' (SMase) is an enzyme which catalyzes the hydrolysis of sphingomyelin (SM) to [http://en.wikipedia.org/wiki/Ceramide ceramide] and [http://en.wikipedia.org/wiki/Phosphocholine phosphocholine]. This enzyme also has [http://en.wikipedia.org/wiki/Hemolytic hemolytic] activity where red blood cells are ruptured and hemoglobin is released into the blood plasma. <ref name="gp">PMID: 16595670 </ref>. SMase is a member of the [http://en.wikipedia.org/wiki/DnaI DNA-I] superfamily involved in hydrolytic cleavage during metabolism reactions. This enzyme has become the object of renewed interest since the discovery of the sphingomyelin [http://en.wikipedia.org/wiki/Signal_transduction signal transduction pathway] which is involved in apoptosis. This pathway is initiated by a neutral sphingomyelinase hydrolysis of sphingomyelin in the plasma membrane to generate ceramide. Ceramide acts as a secondary messenger which causes the stimulation of the cascade effect of kinases and transcription factors which activate programmed cell death<ref name="gp2">PMID: 7544586 </ref>. | ||
==Types of SMase<ref name="gp3">PMID: 12401200 </ref>:== | ==Types of SMase<ref name="gp3">PMID: 12401200 </ref>:== | ||
''Acid sphingomyelinase (aSMase)'' - aSMase is a soluble lysosomal hydrolase with an optical acivity at pH 5. Acid-SMase has two enzymatic forms: one is targeted to the endo-lysosomal compartment where it coordinates Zn, and the other can be realeased extracellularly through the golgi secretory pathway<ref name="gp4">PMID: 21098024 </ref>. A deficiency in results in the lysosomal storage disorder Niemann-Pick disease. Acid-SMase normally metabolizes sphingomyelin which is found in every cell of the body. When aSMase is lacking in the cell, SM builds up and eventually results in cell death<ref name="gp5">PMID: 18567738 </ref>. | ''Acid sphingomyelinase (aSMase)'' - aSMase is a soluble lysosomal hydrolase with an optical acivity at pH 5. Acid-SMase has two enzymatic forms: one is targeted to the endo-lysosomal compartment where it coordinates Zn, and the other can be realeased extracellularly through the golgi secretory pathway<ref name="gp4">PMID: 21098024 </ref>. A deficiency in results in the lysosomal storage disorder [http://en.wikipedia.org/wiki/Niemann%E2%80%93Pick_disease Niemann-Pick disease]. Acid-SMase normally metabolizes sphingomyelin which is found in every cell of the body. When aSMase is lacking in the cell, SM builds up and eventually results in cell death<ref name="gp5">PMID: 18567738 </ref>. | ||
''Secretory sphingomyelinase (S-SMase)'' - S-Smase is found in human vascular endothelial cells and arises from the acid-SMase gene through differential protein trafficking of a precurser. The precurser can be targeted to the Gogli [http://en.wikipedia.org/wiki/Secretory_pathway secretory pathway] or lysosomes. S-SMase hydrolyses (SM) found in plasma membranes and lipoprotein molecules but has also been found to play an important role in intracellular or paracrine ceramide second messenger signaling pathways. S-SMase is activated by normal levels of Zn2+ and operates generally at acidic pH levels, but can hydrolyze atherogenic lipoproteins at neutral pH<ref name="gp6">PMID: 11001566 </ref>. | ''Secretory sphingomyelinase (S-SMase)'' - S-Smase is found in human vascular endothelial cells and arises from the acid-SMase gene through differential protein trafficking of a precurser. The precurser can be targeted to the Gogli [http://en.wikipedia.org/wiki/Secretory_pathway secretory pathway] or lysosomes. S-SMase hydrolyses (SM) found in plasma membranes and lipoprotein molecules but has also been found to play an important role in intracellular or paracrine ceramide second messenger signaling pathways. S-SMase is activated by normal levels of Zn2+ and operates generally at acidic pH levels, but can hydrolyze atherogenic lipoproteins at neutral pH<ref name="gp6">PMID: 11001566 </ref>. | ||