neutral ceramidase (NCDase, N-CDase, acylsphingosine deacylase 2, N-acylsphingosine amidohydrolase 2, BCDase, LCDase, hCD, [Contains: Neutral ceramidase soluble form], ASAH2, HNAC1)
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Function
- hydrolyzes the sphingolipid ceramide into sphingosine & free fatty acid at an optimal pH of 6.5-8.5
- regulator of sphingolipid signaling metabolites by generating sphingosine at the cell surface
- repressor of apoptosis both by reducing C16-ceramide, thereby preventing ceramide-induced apoptosis, & generating sphingosine, a precursor of the antiapoptotic factor sphingosine 1-phosphate
- role in digestion of dietary sphingolipids in intestine by acting as a key enzyme for the catabolism of dietary sphingolipids & regulating the levels of bioactive sphingolipid metabolites in the intestinal tract
- phosphorylation may prevent ubiquitination & subsequent degradation (putative)
- ubiquitination leads to its degradation by the proteasome
- ubiquitination is triggered by nitric oxid (putative)
N-acylsphingosine + H2O <--> a carboxylate + sphingosine
Inhibition:
- inhibited by dithiothreitol (DTT), 2-mercaptoethanol, Zn+2, Cu+2 & Fe+2
- KM=71.4 uM for octanoyl-sphingosine
- KM=66 uM for palmitoyl-sphingosine
- Vmax=160 umol/min/mg enzyme with octanoyl-sphingosine
- Vmax=16 umol/min/mg enzyme with palmitoyl-sphingosine
- Optimum pH is 7.5-9.5
Structure
- belongs to the neutral ceramidase family
- N-glycosylated, required for enzyme activity (putative)
- O-glycosylated, required to retain it as a type 2 membrane protein at the cell surface
Compartment
- cell membrane
- neutral ceramidase soluble form is a secreted protein
Alternative splicing
named isoforms=2
Expression
- ubiquitously expressed
- higher levels in kidney, skeletal muscle & heart