Chitotriosidase (Chitinase 1, CHIT1)

Chitotriosidase, also known as Chitinase-1 and CHIT1, is a member of the glycosyl hydrolase 18 family and Chitinase class II subfamily. It is a member of the mammalian chitinase family, structurally homologous to chitinases from other species, is synthesized and secreted by specifically activated macrophages. Chitotriosidase is a polymer of N-acetylglucosamine. Serum and plasma chitotriosidase activity is usually measured as the first step in diagnosis of Gaucher disease. Monitoring chitotriosidase activity is widely used during treatment of this pathology by enzyme replacement therapy. Its elevated plasma level reflects gradual intralysosomal accumulation in Gaucher cells (lipid-loaded macrophages). Macrophages overloaded by the enzyme accumulated in lysosomal material (lipids) were shown to secrete chitotriosidase; its increased expression was noted in several lysosomal storage diseases and atherosclerosis. In addition to lipid storage disorders, where Chit activity has longer been used as a marker of disease activity and therapeutic response, elevation of plasma Chit may occur in hematological disorders with storage of erythrocyte membrane breakdown products as thalassemia and different systemic infectious diseases sustained by fungi and other pathogens. Recently, increased Chit activity was demonstrated in CNS from patients with different neurological disorders. Chitotriosidase is believed to play a role in mechanisms of immunity and protection against chitin-containing pathogens.

Chitotriosidase (Chitinase 1, CHIT1) Related Areas

Enzyme>>Carbohydrate Metabolism Enzymes>>Chitotriosidase/Chitinase 1/CHIT1

Chitotriosidase (Chitinase 1, CHIT1) Alternative Names

Chitotriosidase, Chitinase 1, CHIT1, CHI3, CHIT, FLJ00314, MGC125322 [Homo sapiens]

Chitotriosidase, Chitinase 1, Chit1, 2300002L19Rik [Mus musculus]

Summaries for Chitotriosidase (Chitinase 1, CHIT1)

Entrez Gene summary for CHIT1:

Chitotriosidase is secreted by activated human macrophages and is markedly elevated in plasma of Gaucher disease patients. The expression of chitotriosidase occurs only at a late stage of differentiation of monocytes to activated macrophages in culture. Human macrophages can synthesize a functional chitotriosidase, a highly conserved enzyme with a strongly regulated expression. This enzyme may play a role in the degradation of chitin-containing pathogens. Several alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, Jan 2012]

OMIM - description for Chitotriosidase:

The CHIT1 gene encodes plasma methylumbelliferyl tetra-N-acetylchitotetraoside hydrolase (chitotriosidase), a human chitinase (EC 3.2.1.14). Chitinases play a role in degrading the chitin walls of some microorganisms (Boot et al., 1995).

Human Chitotriosidase (Chitinase 1, CHIT1) Protein General Information

 

• Protein names: Chitotriosidase-1
• Sequence length: 466 AA.
• Catalytic activity: Random hydrolysis of N-acetyl-beta-D-glucosaminide (1->4)-beta-linkages in chitin and chitodextrins.
• Sequence similarities: Chitotriosidase belongs to the glycosyl hydrolase 18 family. Chitinase class II subfamily. Chitotriosidase contains 1 chitin-binding type-2 domain.
• Polymorphism: A 24 bp duplication in exon 10 leads to the activation of an alternative splice site and the production of an inactive protein resulting in chitotriosidase deficiency [MIM:614122]. About 6% of the population are deficient for Chitotriosidase activity, while 35% are carriers and show reduced enzyme levels. People with CHIT1 deficiency appear perfectly healthy.
• Subunit structure: Monomer.
• Subcellular location: Secreted. Lysosome. Note: A small proportion is lysosomal.
• Tissue specificity: Detected in spleen. Secreted by cultured macrophages.
• Miscellaneous: Very high plasma levels of CHIT1 are found in patients with Gaucher disease type 1 (GD I). Chitotriosidase can be used as diagnostic aid and to evaluate the success of treatment that brings levels back to normal.

General information above from UniProt

Function for Chitotriosidase (Chitinase 1, CHIT1) Protein

UniProtKB:

Chitotriosidase degrades chitin, chitotriose and chitobiose. Chitotriosidase may participate in the defense against nematodes and other pathogens. Isoform 3 has no enzymatic activity.

Genatlas:

• hydrolyse chitin
• Chitotriosidase may be playing an important role in the capacity of cells to respond to and cope with changes in their environment
• Chitotriosidase may play a role in the degradation of chitin-containing pathogens (anti-fungal activity towards chitin-containing fungi)
• Chitotriosidase is functional chitinolytic enzyme, associated with several diseases involving macrophage activation (Malaguarnera 2009)

Phenotype Information for Chitotriosidase (Chitinase 1, CHIT1)

• Gene/Locus: CHIT, CHITD
• Phenotype: [Chitotriosidase deficiency]

Phenotype Information for Chitotriosidase from OMIM (Online Mendelian Inheritance in Man)