Target type: molecularfunction
Catalysis of the reaction: H2O + sphingomyelin = ceramide + choline phosphate + H+ in a neutral environment. [GOC:dph, PMID:26493087]
Neutral sphingomyelin phosphodiesterase activity refers to the enzymatic hydrolysis of sphingomyelin, a major phospholipid component of cell membranes, into ceramide and phosphocholine. This reaction is crucial for various cellular processes, including signal transduction, membrane trafficking, and apoptosis.
Neutral sphingomyelin phosphodiesterase, also known as sphingomyelinase D (SMase D), is an enzyme that specifically cleaves the phosphodiester bond between the phosphate group and the choline head group of sphingomyelin. This hydrolysis occurs at neutral pH, distinguishing it from other sphingomyelinases that function at acidic pH.
The catalytic mechanism of SMase D involves a two-step process. First, the enzyme binds to the sphingomyelin substrate. Then, the catalytic site of the enzyme, likely containing a histidine residue, activates a water molecule, which then attacks the phosphodiester bond, leading to the cleavage of the sphingomyelin molecule.
The ceramide product of this reaction acts as a potent signaling molecule, mediating various cellular processes, including apoptosis, cell differentiation, and inflammation. Ceramide can also modulate the physical properties of membranes, altering their fluidity and permeability.
Furthermore, the activity of SMase D is tightly regulated, ensuring that the production of ceramide is balanced and controlled. The enzyme is subject to regulation by various factors, including intracellular calcium levels, reactive oxygen species, and growth factors.
The dysregulation of SMase D activity has been implicated in various pathological conditions, including cancer, neurodegenerative diseases, and inflammatory disorders. For instance, increased SMase D activity has been observed in cancer cells, contributing to their proliferation and survival. Conversely, reduced SMase D activity has been linked to neurodegenerative disorders, such as Alzheimer's disease, due to impaired ceramide production and signaling.'
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| Protein | Definition | Taxonomy |
|---|---|---|
| Sphingomyelin phosphodiesterase 3 | A sphingomyelin phosphodiesterase 3 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q9NY59] | Homo sapiens (human) |
| Compound | Definition | Classes | Roles |
|---|---|---|---|
| cambinol | cambinol: inhibitor of human silent information regulator 2 enzymes; structure in first source |