ASAH1 : N-acylsphingosine amidohydrolase 1

Description

The ASAH1 (N-acylsphingosine amidohydrolase 1) is a protein-coding gene located on chromosome 8.

The ASAH1 gene provides instructions for making an enzyme called acid ceramidase. This enzyme is found in lysosomes, which are cell compartments that digest and recycle materials. Within lysosomes, acid ceramidase breaks down fats (lipids) called ceramides. Ceramides are typically found within the membranes that surround cells and play a role in regulating cell maturation (differentiation), growth and division of cells (proliferation), and controlled cell death (apoptosis). Additionally, ceramides are a component of a fatty substance called myelin that insulates and protects nerve cells. Ceramides also serve as building blocks for more complex lipids. When ceramides need to be replaced, they travel to lysosomes where acid ceramidase breaks them down into a fat called sphingosine and a fatty acid. These two breakdown products are recycled to create new ceramides for the body to use.

ASAH1 encodes acid ceramidase, a lysosomal enzyme that breaks down ceramides into sphingosine and free fatty acids. Ceramides, sphingosine, and its phosphorylated form sphingosine-1-phosphate are bioactive lipids that regulate cellular signaling pathways involved in cell proliferation, apoptosis, and differentiation. ASAH1 exhibits higher catalytic efficiency towards C12-ceramides compared to other ceramides. It also catalyzes the reverse reaction, allowing the synthesis of ceramides from fatty acids and sphingosine. ASAH1 has N-acylethanolamine hydrolase activity. It regulates ceramide, sphingosine, and sphingosine-1-phosphate levels in the epidermis, mediating calcium-induced differentiation of epidermal keratinocytes. It also indirectly regulates tumor necrosis factor/TNF-induced apoptosis. ASAH1 regulates the intracellular balance between ceramides and sphingosine in adrenocortical cells, likely acting as a regulator of steroidogenesis. It may directly regulate steroidogenesis by binding the nuclear receptor NR5A1 and negatively regulating its transcriptional activity. {ECO:0000250|UniProtKB:Q9WV54, ECO:0000269|PubMed:10610716, ECO:0000269|PubMed:11451951, ECO:0000269|PubMed:12764132, ECO:0000269|PubMed:12815059, ECO:0000269|PubMed:15655246, ECO:0000269|PubMed:17713573, ECO:0000269|PubMed:22261821, ECO:0000269|PubMed:7744740, ECO:0000303|PubMed:10610716}

ASAH1 is also known as AC, ACDase, ASAH, PHP, PHP32, SMAPME.

Associated Diseases

Comprehensive carrier screening

WES Whole Exome Sequencing

Clinical Exome Sequencing